期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 38, 页码 E5552-E5561出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1524412113
关键词
F-BAR; actin; Drosophila; Nwk; WASp
资金
- Russian Science Foundation [14-14-00234]
- Pew Scholar Award
- NIH/National Institutes of General Medical Sciences genetics training grant [T32 GM007122]
- Howard Hughes Medical Institute Science Education [52008141]
- Brandeis Center for Bioinspired Soft Materials, a National Science Foundation Materials Research Science and Engineering Center [DMR-1420382]
- Russian Science Foundation [14-14-00234] Funding Source: Russian Science Foundation
Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. On membrane binding, Nwk SH3 domains do not completely dissociate from the F-BAR dimer, but instead shift from its concave surface to positions on either side of the dimer. Unexpectedly, along with controlling membrane binding, these autoregulatory interactions inhibit the ability of Nwk-SH3a to activate Wiskott-Aldrich syndrome protein (WASp)/actin related protein (Arp) 2/3-dependent actin filament assembly. In Drosophila neurons, Nwk autoregulation restricts SH3a domain-dependent synaptopod formation, synaptic growth, and actin organization. Our results define structural rearrangements in Nwk that control F-BAR-membrane interactions as well as SH3 domain activities, and suggest that these two functions are tightly coordinated in vitro and in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据