3a5n | pdb_00003a5n
Crystal Structure of a Dictyostelium P109A Ca2+-Actin in Complex with Human Gelsolin Segment 1
Structural highlights
Disease[GELS_HUMAN] Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:105120]; also known as familial amyloidosis Finnish type. AMYL5 is a hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure.[1] [2] [3] [4] Function[GELS_HUMAN] Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.[5] Publication Abstract from PubMedAssembled actin filaments support cellular signaling, intracellular trafficking, and cytokinesis. ATP hydrolysis triggered by actin assembly provides the structural cues for filament turnover in vivo. Here, we present the cryo-electron microscopic (cryo-EM) structure of filamentous actin (F-actin) in the presence of phosphate, with the visualization of some alpha-helical backbones and large side chains. A complete atomic model based on the EM map identified intermolecular interactions mediated by bound magnesium and phosphate ions. Comparison of the F-actin model with G-actin monomer crystal structures reveals a critical role for bending of the conserved proline-rich loop in triggering phosphate release following ATP hydrolysis. Crystal structures of G-actin show that mutations in this loop trap the catalytic site in two intermediate states of the ATPase cycle. The combined structural information allows us to propose a detailed molecular mechanism for the biochemical events, including actin polymerization and ATPase activation, critical for actin filament dynamics. Structural basis for actin assembly, activation of ATP hydrolysis, and delayed phosphate release.,Murakami K, Yasunaga T, Noguchi TQ, Gomibuchi Y, Ngo KX, Uyeda TQ, Wakabayashi T Cell. 2010 Oct 15;143(2):275-87. PMID:20946985[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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