Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex

• 成果类型: Article
• 署名作者: Guo, Qian; Chen, Kai-en; Gimenez-Andres, Manuel; Jellett, Adam P.; Gao, Ya; Simonetti, Boris; Liu, Meihan; Danson, Chris M.; Heesom, Kate J.; Cullen, Peter J.; Collins, Brett M.
• 署名单位: University of Queensland; University of Bristol; University of Bristol
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14158
• DOI: 10.1073/pnas.2405041121
• 发表日期: 2024-08-13
• 关键词: membrane recruitment; potassium channels; arp2/3 activator; plasma-membrane; pdz domain; retromer; actin; TRAFFICKING; proteins; binding

摘要

Endosomal membrane trafficking is mediated by specific protein coats and formation of actin- rich membrane domains. The Retromer complex coordinates with sorting nexin (SNX) cargo adaptors including SNX27, and the SNX27-Retromer assembly interacts with the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex which nucleates actin filaments establishing the endosomal recycling domain. Crystal structures, modeling, biochemical, and cellular validation reveal how the FAM21 subunit of WASH interacts with both Retromer and SNX27. FAM21 binds the FERM the SNX1 and SNX2 subunits of the ESCPE- 1 complex. Overlapping FAM21 repeats and a specific Pro- Leu containing motif bind three distinct sites on Retromer involving both the VPS35 and VPS29 subunits. Mutation of the major VPS35- binding site does indicating that a network of redundant interactions promote endosomal activity of the tions required for the dynamic assembly of endosomal membrane recycling domains.