| Literature DB >> 26073603 |
Morten L Karlsen1, Thor S Thorsen1, Niklaus Johner2, Ina Ammendrup-Johnsen1, Simon Erlendsson1,3, Xinsheng Tian4, Jens B Simonsen5, Rasmus Høiberg-Nielsen5, Nikolaj M Christensen1, George Khelashvili2, Werner Streicher6, Kaare Teilum3, Bente Vestergaard4, Harel Weinstein2, Ulrik Gether1, Lise Arleth5, Kenneth L Madsen1.
Abstract
PICK1 is a neuronal scaffolding protein containing a PDZ domain and an auto-inhibited BAR domain. BAR domains are membrane-sculpting protein modules generating membrane curvature and promoting membrane fission. Previous data suggest that BAR domains are organized in lattice-like arrangements when stabilizing membranes but little is known about structural organization of BAR domains in solution. Through a small-angle X-ray scattering (SAXS) analysis, we determine the structure of dimeric and tetrameric complexes of PICK1 in solution. SAXS and biochemical data reveal a strong propensity of PICK1 to form higher-order structures, and SAXS analysis suggests an offset, parallel mode of BAR-BAR oligomerization. Furthermore, unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. Together with functional data, these structural findings are compatible with a model in which oligomerization governs auto-inhibition of BAR domain function.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26073603 PMCID： PMC4502314 DOI： 10.1016/j.str.2015.04.020
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006