2009年8月
The crystal structure of the C-terminus of adseverin reveals the actin-binding interface
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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- 巻
- 106
- 号
- 33
- 開始ページ
- 13719
- 終了ページ
- 13724
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.0812383106
- 出版者・発行元
- NATL ACAD SCIENCES
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.
- リンク情報
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- DOI
- https://doi.org/10.1073/pnas.0812383106
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/19666531
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000269078700019&DestApp=WOS_CPL
- URL
- http://orcid.org/0000-0001-6367-6903
- ID情報
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- DOI : 10.1073/pnas.0812383106
- ISSN : 0027-8424
- ORCIDのPut Code : 18082999
- PubMed ID : 19666531
- Web of Science ID : WOS:000269078700019