@article {2395, title = {The crystal structure of the C-terminus of adseverin reveals the actin-binding interface}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {33}, year = {2009}, note = {ISI Document Delivery No.: 484WETimes Cited: 0Cited Reference Count: 21Chumnarnsilpa, Sakesit Lee, Wei Lin Nag, Shalini Kannan, Balakrishnan Larsson, Marten Burtnick, Leslie D. Robinson, Robert C.}, month = {Aug}, pages = {13719-13724}, type = {Article}, abstract = {Adseverin is a member of the calcium-regulated gelsolin superfamily of actin severing and capping proteins. Adseverin comprises 6 homologous domains (A1-A6), which share 60\% identity with the 6 domains from gelsolin (G1-G6). Adseverin is truncated in comparison to gelsolin, lacking the C-terminal extension that masks the F-actin binding site in calcium-free gelsolin. Biochemical assays have indicated differences in the interaction of the C-terminal halves of adseverin and gelsolin with actin. Gelsolin contacts actin through a major site on G4 and a minor site on G6, whereas adseverin uses a site on A5. Here, we present the X-ray structure of the activated C-terminal half of adseverin (A4-A6). This structure is highly similar to that of the activated form of the C-terminal half of gelsolin (G4-G6), both in arrangement of domains and in the 3 bound calcium ions. Comparative analysis of the actin-binding surfaces observed in the G4-G6/actin structure suggests that adseverin in this conformation will also be able to interact with actin through A4 and A6, whereas the A5 surface is obscured. A single residue mutation in A4-A6 located at the predicted A4/actin interface completely abrogates actin sequestration. A model of calcium-free adseverin, constructed from the structure of gelsolin, predicts that in the absence of a gelsolin-like C-terminal extension the interaction between A2 and A6 provides the steric inhibition to prevent interaction with F-actin. We propose that calcium binding to the N terminus of adseverin dominates the activation process to expose the F-actin binding site on A2.}, keywords = {74-KDA PROTEIN, ACTIVATION, calcium activated, EXOCYTOSIS, gelsolin, HALF, LOCALIZATION, SCINDERIN, SITE, TIRF}, isbn = {0027-8424}, url = {://000269078700019}, author = {Chumnarnsilpa, S. and Lee, W. L. and Nag, S. and Kannan, B. and Larsson, M. and Burtnick, L. D. and Robinson, R. C.} }