2n8y

Holo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1Holo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1

Structural highlights 2n8y is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACTN1_HUMAN F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Publication Abstract from PubMed The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is alpha-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of alpha-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle alpha-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other alpha-actinins, we provide a structural model of regulation of the actin crosslinking activity of alpha-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin. Structure and calcium-binding studies of calmodulin-like domain of human non-muscle alpha-actinin-1.,Drmota Prebil S, Slapsak U, Pavsic M, Ilc G, Puz V, de Almeida Ribeiro E, Anrather D, Hartl M, Backman L, Plavec J, Lenarcic B, Djinovic-Carugo K Sci Rep. 2016 Jun 7;6:27383. doi: 10.1038/srep27383. PMID:27272015 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Actinin 3D structures

spinqualitylabelsall models 2n8y Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image