From the first to the second domain of gelsolin: a common path on the surface of actin?
We present the 2.6 A resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25-Gln160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin-actin contacts. Alignment of the sequence of the structurally important residues within the G1-G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott-Aldridge syndrome protein) and thymosin beta4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin.
Irobi
Edward
E
Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, 751 23 Uppsala, Sweden.
Burtnick
Leslie D
LD
Urosev
Dunja
D
Narayan
Kartik
K
Robinson
Robert C
RC
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018260:Gelsolin / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D018260:Gelsolin; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011994:Recombinant Proteins