Structure of gelsolin segment 1-actin complex and the mechanism of filament severing

Abstract

The structure of the segment 1 domain of gelsolin, a protein that fragments actin filaments in cells, is reported in complex with actin. Segment 1 binds monomer using an apolar patch rimmed by hydrogen bonds in a cleft between actin domains. On the actin filament model it binds tangentially, disrupting only those contacts between adjacent subunits in one helical strand. The segment 1 fold is general for all segments of the gelsolin family because the conserved residues form the core of the structure. It also provides a basis for understanding the origin of an amyloidosis caused by a gelsolin variant.

Conformational changes in subdomain I of actin induced by proteolytic cleavage within the DNase I‐binding loop: energy transfer from tryptophan to AEDANS

“…3) in the processes of the energy transfer. Analysis of the spatial structure of actin [12,13] has revealed that all tryptophan residues are not farther than 20 .~ from the C-terminal residue 372 and can contribute to the energy transfer. At the same time, these four tryptophan residues are located in different microenvironments: Trp-340 and Trp-356 are buried while Trp-79 and Trp-86 are partially exposed.…”

Platelet Microvesicles (Microparticles) in Cardiac Surgery

“…17,18 In addition to the loss of membrane asymmetry, activation of gelsolin and calpain causes is alteration of the platelet actin cytoskeleton and a change in platelet shape, which in itself produces PMV. 19,20 However, PMV are still produced when calpain is inhibited. 21 There are consequentially multiple pathways to PMV production, and disabling one pathway may still allow PMV to be shed.…”

Refined structure of villin 14T and a detailed comparison with other actin‐severing domains

“…The glycines and prolines important for delineating elements of secondary structure are shown in green. Side chains that provide calcium ligands, based on the structure of gelsolin segment 1 in a co-crystal with actin (McLaughlin et al, 1993). are shown in gold outlined letters.…”

“…The three-dimensional structure of gelsolin segment 1 in a complex with actin has been solved by X-ray crystallography (McLaughlin et al, 1993). The structure of the first domain of villin has been solved in solution by NMR (Markus et al, 1994a), as has the structured core of the seventh domain (C. J.…”

“…Many of the residues within the most strongly conserved region contribute to the hydrophobic core of the molecule and to the turns between elements of secondary structure and thus are conserved for structural rather than functional reasons. Calcium is bound in two places in the gelsolin segment 1-actin co-crystal, an intramolecular site, with ligands from side chains from the second helix and a loop between two /?-strands as well as from two backbone carbonyls, and an intermolecular site, with some ligands from the actin monomer (McLaughlin et al, 1993). Chemical shift evidence suggests similar binding sites in villin 14T (Markus et al, 1994a) and severin domain 1 (Schnuchel et al, 1995).…”