Article open access publication

Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering

Structure, Elsevier, ISSN 0969-2126

Volume 23, 7, 2015

DOI:10.1016/j.str.2015.04.020, Dimensions: pub.1047827660, PMC: PMC4502314, PMID: 26073603,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Cornell University, grid.5386.8

Description

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.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2015: Blocked

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 18

Field Citation Ratio (FCR): 2.74

Relative Citation ratio (RCR): 0.98

Open Access Info

Hybrid