@article{7697, abstract = {* Morphogenesis and adaptive tropic growth in plants depend on gradients of the phytohormone auxin, mediated by the membrane‐based PIN‐FORMED (PIN) auxin transporters. PINs localize to a particular side of the plasma membrane (PM) or to the endoplasmic reticulum (ER) to directionally transport auxin and maintain intercellular and intracellular auxin homeostasis, respectively. However, the molecular cues that confer their diverse cellular localizations remain largely unknown. * In this study, we systematically swapped the domains between ER‐ and PM‐localized PIN proteins, as well as between apical and basal PM‐localized PINs from Arabidopsis thaliana , to shed light on why PIN family members with similar topological structures reside at different membrane compartments within cells. * Our results show that not only do the N‐ and C‐terminal transmembrane domains (TMDs) and central hydrophilic loop contribute to their differential subcellular localizations and cellular polarity, but that the pairwise‐matched N‐ and C‐terminal TMDs resulting from intramolecular domain–domain coevolution are also crucial for their divergent patterns of localization. * These findings illustrate the complexity of the evolutionary path of PIN proteins in acquiring their plethora of developmental functions and adaptive growth in plants.}, author = {Zhang, Yuzhou and Hartinger, Corinna and Wang, Xiaojuan and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {5}, pages = {1406--1416}, publisher = {Wiley}, title = {{Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters}}, doi = {10.1111/nph.16629}, volume = {227}, year = {2020}, } @article{7707, abstract = {The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Quantification of the overall contribution of gene-environment interaction for obesity-related traits}}, doi = {10.1038/s41467-020-15107-0}, volume = {11}, year = {2020}, } @article{7708, abstract = {We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.}, author = {Nabais, Marta F. and Lin, Tian and Benyamin, Beben and Williams, Kelly L. and Garton, Fleur C. and Vinkhuyzen, Anna A. E. and Zhang, Futao and Vallerga, Costanza L. and Restuadi, Restuadi and Freydenzon, Anna and Zwamborn, Ramona A. J. and Hop, Paul J. and Robinson, Matthew Richard and Gratten, Jacob and Visscher, Peter M. and Hannon, Eilis and Mill, Jonathan and Brown, Matthew A. and Laing, Nigel G. and Mather, Karen A. and Sachdev, Perminder S. and Ngo, Shyuan T. and Steyn, Frederik J. and Wallace, Leanne and Henders, Anjali K. and Needham, Merrilee and Veldink, Jan H. and Mathers, Susan and Nicholson, Garth and Rowe, Dominic B. and Henderson, Robert D. and McCombe, Pamela A. and Pamphlett, Roger and Yang, Jian and Blair, Ian P. and McRae, Allan F. and Wray, Naomi R.}, issn = {2056-7944}, journal = {npj Genomic Medicine}, publisher = {Springer Nature}, title = {{Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis}}, doi = {10.1038/s41525-020-0118-3}, volume = {5}, year = {2020}, } @article{5681, abstract = {We introduce dynamically warping grids for adaptive liquid simulation. Our primary contributions are a strategy for dynamically deforming regular grids over the course of a simulation and a method for efficiently utilizing these deforming grids for liquid simulation. Prior work has shown that unstructured grids are very effective for adaptive fluid simulations. However, unstructured grids often lead to complicated implementations and a poor cache hit rate due to inconsistent memory access. Regular grids, on the other hand, provide a fast, fixed memory access pattern and straightforward implementation. Our method combines the advantages of both: we leverage the simplicity of regular grids while still achieving practical and controllable spatial adaptivity. We demonstrate that our method enables adaptive simulations that are fast, flexible, and robust to null-space issues. At the same time, our method is simple to implement and takes advantage of existing highly-tuned algorithms.}, author = {Hikaru, Ibayashi and Wojtan, Christopher J and Thuerey, Nils and Igarashi, Takeo and Ando, Ryoichi}, issn = {19410506}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {6}, pages = {2288--2302}, publisher = {IEEE}, title = {{Simulating liquids on dynamically warping grids}}, doi = {10.1109/TVCG.2018.2883628}, volume = {26}, year = {2020}, } @article{6184, abstract = {We prove edge universality for a general class of correlated real symmetric or complex Hermitian Wigner matrices with arbitrary expectation. Our theorem also applies to internal edges of the self-consistent density of states. In particular, we establish a strong form of band rigidity which excludes mismatches between location and label of eigenvalues close to internal edges in these general models.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {0091-1798}, journal = {Annals of Probability}, number = {2}, pages = {963--1001}, publisher = {Institute of Mathematical Statistics}, title = {{Correlated random matrices: Band rigidity and edge universality}}, doi = {10.1214/19-AOP1379}, volume = {48}, year = {2020}, } @article{6185, abstract = {For complex Wigner-type matrices, i.e. Hermitian random matrices with independent, not necessarily identically distributed entries above the diagonal, we show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are universal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner–Dyson–Mehta universality conjecture for the last remaining universality type in the complex Hermitian class. Our analysis holds not only for exact cusps, but approximate cusps as well, where an extended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp for both symmetry classes. This result is also the key input in the companion paper (Cipolloni et al. in Pure Appl Anal, 2018. arXiv:1811.04055) where the cusp universality for real symmetric Wigner-type matrices is proven. The novel cusp fluctuation mechanism is also essential for the recent results on the spectral radius of non-Hermitian random matrices (Alt et al. in Spectral radius of random matrices with independent entries, 2019. arXiv:1907.13631), and the non-Hermitian edge universality (Cipolloni et al. in Edge universality for non-Hermitian random matrices, 2019. arXiv:1908.00969).}, author = {Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, pages = {1203--1278}, publisher = {Springer Nature}, title = {{Cusp universality for random matrices I: Local law and the complex Hermitian case}}, doi = {10.1007/s00220-019-03657-4}, volume = {378}, year = {2020}, } @article{6358, abstract = {We study dynamical optimal transport metrics between density matricesassociated to symmetric Dirichlet forms on finite-dimensional C∗-algebras. Our settingcovers arbitrary skew-derivations and it provides a unified framework that simultaneously generalizes recently constructed transport metrics for Markov chains, Lindblad equations, and the Fermi Ornstein–Uhlenbeck semigroup. We develop a non-nommutative differential calculus that allows us to obtain non-commutative Ricci curvature bounds, logarithmic Sobolev inequalities, transport-entropy inequalities, andspectral gap estimates.}, author = {Carlen, Eric A. and Maas, Jan}, issn = {15729613}, journal = {Journal of Statistical Physics}, number = {2}, pages = {319--378}, publisher = {Springer Nature}, title = {{Non-commutative calculus, optimal transport and functional inequalities in dissipative quantum systems}}, doi = {10.1007/s10955-019-02434-w}, volume = {178}, year = {2020}, } @article{6359, abstract = {The strong rate of convergence of the Euler-Maruyama scheme for nondegenerate SDEs with irregular drift coefficients is considered. In the case of α-Hölder drift in the recent literature the rate α/2 was proved in many related situations. By exploiting the regularising effect of the noise more efficiently, we show that the rate is in fact arbitrarily close to 1/2 for all α>0. The result extends to Dini continuous coefficients, while in d=1 also to all bounded measurable coefficients.}, author = {Dareiotis, Konstantinos and Gerencser, Mate}, issn = {1083-6489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{On the regularisation of the noise for the Euler-Maruyama scheme with irregular drift}}, doi = {10.1214/20-EJP479}, volume = {25}, year = {2020}, } @article{6488, abstract = {We prove a central limit theorem for the difference of linear eigenvalue statistics of a sample covariance matrix W˜ and its minor W. We find that the fluctuation of this difference is much smaller than those of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of W˜ and W. Our result identifies the fluctuation of the spatial derivative of the approximate Gaussian field in the recent paper by Dumitru and Paquette. Unlike in a similar result for Wigner matrices, for sample covariance matrices, the fluctuation may entirely vanish.}, author = {Cipolloni, Giorgio and Erdös, László}, issn = {20103271}, journal = {Random Matrices: Theory and Application}, number = {3}, publisher = {World Scientific Publishing}, title = {{Fluctuations for differences of linear eigenvalue statistics for sample covariance matrices}}, doi = {10.1142/S2010326320500069}, volume = {9}, year = {2020}, } @article{6563, abstract = {This paper presents two algorithms. The first decides the existence of a pointed homotopy between given simplicial maps 𝑓,𝑔:𝑋→𝑌, and the second computes the group [𝛴𝑋,𝑌]∗ of pointed homotopy classes of maps from a suspension; in both cases, the target Y is assumed simply connected. More generally, these algorithms work relative to 𝐴⊆𝑋.}, author = {Filakovský, Marek and Vokřínek, Lukas}, issn = {16153383}, journal = {Foundations of Computational Mathematics}, pages = {311--330}, publisher = {Springer Nature}, title = {{Are two given maps homotopic? An algorithmic viewpoint}}, doi = {10.1007/s10208-019-09419-x}, volume = {20}, year = {2020}, } @article{6593, abstract = {We consider the monotone variational inequality problem in a Hilbert space and describe a projection-type method with inertial terms under the following properties: (a) The method generates a strongly convergent iteration sequence; (b) The method requires, at each iteration, only one projection onto the feasible set and two evaluations of the operator; (c) The method is designed for variational inequality for which the underline operator is monotone and uniformly continuous; (d) The method includes an inertial term. The latter is also shown to speed up the convergence in our numerical results. A comparison with some related methods is given and indicates that the new method is promising.}, author = {Shehu, Yekini and Li, Xiao-Huan and Dong, Qiao-Li}, issn = {1572-9265}, journal = {Numerical Algorithms}, pages = {365--388}, publisher = {Springer Nature}, title = {{An efficient projection-type method for monotone variational inequalities in Hilbert spaces}}, doi = {10.1007/s11075-019-00758-y}, volume = {84}, year = {2020}, } @inproceedings{14326, abstract = {Learning object-centric representations of complex scenes is a promising step towards enabling efficient abstract reasoning from low-level perceptual features. Yet, most deep learning approaches learn distributed representations that do not capture the compositional properties of natural scenes. In this paper, we present the Slot Attention module, an architectural component that interfaces with perceptual representations such as the output of a convolutional neural network and produces a set of task-dependent abstract representations which we call slots. These slots are exchangeable and can bind to any object in the input by specializing through a competitive procedure over multiple rounds of attention. We empirically demonstrate that Slot Attention can extract object-centric representations that enable generalization to unseen compositions when trained on unsupervised object discovery and supervised property prediction tasks. }, author = {Locatello, Francesco and Weissenborn, Dirk and Unterthiner, Thomas and Mahendran, Aravindh and Heigold, Georg and Uszkoreit, Jakob and Dosovitskiy, Alexey and Kipf, Thomas}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713829546}, location = {Virtual}, pages = {11525--11538}, publisher = {Curran Associates}, title = {{Object-centric learning with slot attention}}, volume = {33}, year = {2020}, } @misc{14592, abstract = {Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights into biological processes and structures within a native context. However, a major challenge still lies in the efficient and reproducible preparation of adherent cells for subsequent cryo-EM analysis. This is due to the sensitivity of many cellular specimens to the varying seeding and culturing conditions required for EM experiments, the often limited amount of cellular material and also the fragility of EM grids and their substrate. Here, we present low-cost and reusable 3D printed grid holders, designed to improve specimen preparation when culturing challenging cellular samples directly on grids. The described grid holders increase cell culture reproducibility and throughput, and reduce the resources required for cell culturing. We show that grid holders can be integrated into various cryo-EM workflows, including micro-patterning approaches to control cell seeding on grids, and for generating samples for cryo-focused ion beam milling and cryo-electron tomography experiments. Their adaptable design allows for the generation of specialized grid holders customized to a large variety of applications.}, author = {Schur, Florian KM}, publisher = {Institute of Science and Technology Austria}, title = {{STL-files for 3D-printed grid holders described in Fäßler F, Zens B, et al.; 3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy}}, doi = {10.15479/AT:ISTA:14592}, year = {2020}, } @article{14694, abstract = {We study the unique solution m of the Dyson equation \( -m(z)^{-1} = z\1 - a + S[m(z)] \) on a von Neumann algebra A with the constraint Imm≥0. Here, z lies in the complex upper half-plane, a is a self-adjoint element of A and S is a positivity-preserving linear operator on A. We show that m is the Stieltjes transform of a compactly supported A-valued measure on R. Under suitable assumptions, we establish that this measure has a uniformly 1/3-Hölder continuous density with respect to the Lebesgue measure, which is supported on finitely many intervals, called bands. In fact, the density is analytic inside the bands with a square-root growth at the edges and internal cubic root cusps whenever the gap between two bands vanishes. The shape of these singularities is universal and no other singularity may occur. We give a precise asymptotic description of m near the singular points. These asymptotics generalize the analysis at the regular edges given in the companion paper on the Tracy-Widom universality for the edge eigenvalue statistics for correlated random matrices [the first author et al., Ann. Probab. 48, No. 2, 963--1001 (2020; Zbl 1434.60017)] and they play a key role in the proof of the Pearcey universality at the cusp for Wigner-type matrices [G. Cipolloni et al., Pure Appl. Anal. 1, No. 4, 615--707 (2019; Zbl 07142203); the second author et al., Commun. Math. Phys. 378, No. 2, 1203--1278 (2020; Zbl 07236118)]. We also extend the finite dimensional band mass formula from [the first author et al., loc. cit.] to the von Neumann algebra setting by showing that the spectral mass of the bands is topologically rigid under deformations and we conclude that these masses are quantized in some important cases.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, issn = {1431-0643}, journal = {Documenta Mathematica}, keywords = {General Mathematics}, pages = {1421--1539}, publisher = {EMS Press}, title = {{The Dyson equation with linear self-energy: Spectral bands, edges and cusps}}, doi = {10.4171/dm/780}, volume = {25}, year = {2020}, } @article{14891, abstract = {We give the first mathematically rigorous justification of the local density approximation in density functional theory. We provide a quantitative estimate on the difference between the grand-canonical Levy–Lieb energy of a given density (the lowest possible energy of all quantum states having this density) and the integral over the uniform electron gas energy of this density. The error involves gradient terms and justifies the use of the local density approximation in the situation where the density is very flat on sufficiently large regions in space.}, author = {Lewin, Mathieu and Lieb, Elliott H. and Seiringer, Robert}, issn = {2578-5885}, journal = {Pure and Applied Analysis}, number = {1}, pages = {35--73}, publisher = {Mathematical Sciences Publishers}, title = {{ The local density approximation in density functional theory}}, doi = {10.2140/paa.2020.2.35}, volume = {2}, year = {2020}, } @article{15036, abstract = {The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.}, author = {Rosa, Higor Vinícius Dias and Leonardo, Diego Antonio and Brognara, Gabriel and Brandão-Neto, José and D'Muniz Pereira, Humberto and Araújo, Ana Paula Ulian and Garratt, Richard Charles}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology, Structural Biology}, number = {21}, pages = {5784--5801}, publisher = {Elsevier}, title = {{Molecular recognition at septin interfaces: The switches hold the key}}, doi = {10.1016/j.jmb.2020.09.001}, volume = {432}, year = {2020}, } @article{15037, abstract = {Protein abundance and localization at the plasma membrane (PM) shapes plant development and mediates adaptation to changing environmental conditions. It is regulated by ubiquitination, a post-translational modification crucial for the proper sorting of endocytosed PM proteins to the vacuole for subsequent degradation. To understand the significance and the variety of roles played by this reversible modification, the function of ubiquitin receptors, which translate the ubiquitin signature into a cellular response, needs to be elucidated. In this study, we show that TOL (TOM1-like) proteins function in plants as multivalent ubiquitin receptors, governing ubiquitinated cargo delivery to the vacuole via the conserved Endosomal Sorting Complex Required for Transport (ESCRT) pathway. TOL2 and TOL6 interact with components of the ESCRT machinery and bind to K63-linked ubiquitin via two tandemly arranged conserved ubiquitin-binding domains. Mutation of these domains results not only in a loss of ubiquitin binding but also altered localization, abolishing TOL6 ubiquitin receptor activity. Function and localization of TOL6 is itself regulated by ubiquitination, whereby TOL6 ubiquitination potentially modulates degradation of PM-localized cargoes, assisting in the fine-tuning of the delicate interplay between protein recycling and downregulation. Taken together, our findings demonstrate the function and regulation of a ubiquitin receptor that mediates vacuolar degradation of PM proteins in higher plants.}, author = {Moulinier-Anzola, Jeanette and Schwihla, Maximilian and De-Araújo, Lucinda and Artner, Christina and Jörg, Lisa and Konstantinova, Nataliia and Luschnig, Christian and Korbei, Barbara}, issn = {1674-2052}, journal = {Molecular Plant}, keywords = {Plant Science, Molecular Biology}, number = {5}, pages = {717--731}, publisher = {Elsevier}, title = {{TOLs function as ubiquitin receptors in the early steps of the ESCRT pathway in higher plants}}, doi = {10.1016/j.molp.2020.02.012}, volume = {13}, year = {2020}, } @article{15055, abstract = {Markov decision processes (MDPs) are the defacto framework for sequential decision making in the presence of stochastic uncertainty. A classical optimization criterion for MDPs is to maximize the expected discounted-sum payoff, which ignores low probability catastrophic events with highly negative impact on the system. On the other hand, risk-averse policies require the probability of undesirable events to be below a given threshold, but they do not account for optimization of the expected payoff. We consider MDPs with discounted-sum payoff with failure states which represent catastrophic outcomes. The objective of risk-constrained planning is to maximize the expected discounted-sum payoff among risk-averse policies that ensure the probability to encounter a failure state is below a desired threshold. Our main contribution is an efficient risk-constrained planning algorithm that combines UCT-like search with a predictor learned through interaction with the MDP (in the style of AlphaZero) and with a risk-constrained action selection via linear programming. We demonstrate the effectiveness of our approach with experiments on classical MDPs from the literature, including benchmarks with an order of 106 states.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Novotný, Petr and Vahala, Jiří}, issn = {2374-3468}, journal = {Proceedings of the 34th AAAI Conference on Artificial Intelligence}, keywords = {General Medicine}, location = {New York, NY, United States}, number = {06}, pages = {9794--9801}, publisher = {Association for the Advancement of Artificial Intelligence}, title = {{Reinforcement learning of risk-constrained policies in Markov decision processes}}, doi = {10.1609/aaai.v34i06.6531}, volume = {34}, year = {2020}, } @article{15057, abstract = {Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between C. elegans and humans.}, author = {Park, Sangsoon and Artan, Murat and Han, Seung Hyun and Park, Hae-Eun H. and Jung, Yoonji and Hwang, Ara B. and Shin, Won Sik and Kim, Kyong-Tai and Lee, Seung-Jae V.}, issn = {2375-2548}, journal = {Science Advances}, number = {27}, publisher = {American Association for the Advancement of Science}, title = {{VRK-1 extends life span by activation of AMPK via phosphorylation}}, doi = {10.1126/sciadv.aaw7824}, volume = {6}, year = {2020}, } @article{15061, abstract = {The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.}, author = {Pinotsis, Nikos and Zielinska, Karolina and Babuta, Mrigya and Arolas, Joan L. and Kostan, Julius and Khan, Muhammad Bashir and Schreiner, Claudia and Testa Salmazo, Anita P and Ciccarelli, Luciano and Puchinger, Martin and Gkougkoulia, Eirini A. and Ribeiro, Euripedes de Almeida and Marlovits, Thomas C. and Bhattacharya, Alok and Djinovic-Carugo, Kristina}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {36}, pages = {22101--22112}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin}}, doi = {10.1073/pnas.1917269117}, volume = {117}, year = {2020}, }