학술논문
Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering.
Document Type
Article
Author
Karlsen, Morten L.; Thorsen, Thor S.; Johner, Niklaus; Ammendrup-Johnsen, Ina; Erlendsson, Simon; Tian, Xinsheng; Simonsen, Jens B.; Høiberg-Nielsen, Rasmus; Christensen, Nikolaj M.; Khelashvili, George; Streicher, Werner; Teilum, Kaare; Vestergaard, Bente; Weinstein, Harel; Gether, Ulrik; Arleth, Lise; Madsen, Kenneth L.
Source
Subject
*DIMERIC ions
*CONFORMATIONAL analysis
*PROTEIN structure
*COMPLEX compounds
*X-ray scattering
*MEMBRANE proteins
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Language
ISSN
0969-2126
Abstract
Summary 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. [ABSTRACT FROM AUTHOR]