5nl6 | pdb_00005nl6

The crystal structure of the two spectrin repeat domains from Entamoeba histolytica

spinqualitylabelsall models 5nl6, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nl6 is a 2 chain structure with sequence from Entamoeba histolytica HM-1:IMSS. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.05Å Ligands: BME Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function N9TIJ7_ENTH1 Publication Abstract from PubMed The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin-binding proteins, is fundamentally important in eukaryotes. alpha-Actinins are major F-actin bundlers that are inhibited by Ca(2+) in nonmuscle cells. Here we report the mechanism of Ca(2+)-mediated regulation of Entamoeba histolytica alpha-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic alpha-actinins. Crystal structures of Ca(2+)-free and Ca(2+)-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 Ca(2+), binding of which can only be regulated in the presence of physiological concentrations of Mg(2+) Ca(2+) 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. Calcium modulates the domain flexibility and function of an alpha-actinin similar to the ancestral alpha-actinin.,Pinotsis N, Zielinska K, Babuta M, Arolas JL, Kostan J, Khan MB, Schreiner C, Salmazo A, Ciccarelli L, Puchinger M, Gkougkoulia EA, Ribeiro EA Jr, Marlovits TC, Bhattacharya A, Djinovic-Carugo K Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22101-22112. doi:, 10.1073/pnas.1917269117. Epub 2020 Aug 26. PMID:32848067 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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