Structural basis for membrane binding specificity of the Bin/Amphiphysin/Rvs (BAR) domain of Arfaptin-2 determined by Arl1 GTPase

Kensuke Nakamura; Zhiqiu Man; Yong Xie; Ayako Hanai; Hisayoshi Makyio; Masato Kawasaki; Ryuichi Kato; Hye-Won Shin; Kazuhisa Nakayama; Soichi Wakatsuki

doi:10.1074/jbc.M112.365783

Structural basis for membrane binding specificity of the Bin/Amphiphysin/Rvs (BAR) domain of Arfaptin-2 determined by Arl1 GTPase

J Biol Chem. 2012 Jul 20;287(30):25478-89. doi: 10.1074/jbc.M112.365783. Epub 2012 Jun 7.

Authors

Kensuke Nakamura¹, Zhiqiu Man, Yong Xie, Ayako Hanai, Hisayoshi Makyio, Masato Kawasaki, Ryuichi Kato, Hye-Won Shin, Kazuhisa Nakayama, Soichi Wakatsuki

Affiliation

¹ Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, KEK, Tsukuba, Ibaraki 305-0801, Japan.

Abstract

Membrane-sculpting BAR (Bin/Amphiphysin/Rvs) domains form a crescent-shaped homodimer that can sense and induce membrane curvature through its positively charged concave face. We have recently shown that Arfaptin-2, which was originally identified as a binding partner for the Arf and Rac1 GTPases, binds to Arl1 through its BAR domain and is recruited onto Golgi membranes. There, Arfaptin-2 induces membrane tubules. Here, we report the crystal structure of the Arfaptin-2 BAR homodimer in complex with two Arl1 molecules bound symmetrically to each side, leaving the concave face open for membrane association. The overall structure of the Arl1·Arfaptin-2 BAR complex closely resembles that of the PX-BAR domain of sorting nexin 9, suggesting similar mechanisms underlying BAR domain targeting to specific organellar membranes. The Arl1·Arfaptin-2 BAR structure suggests that one of the two Arl1 molecules competes with Rac1, which binds to the concave face of the Arfaptin-2 BAR homodimer and may hinder its membrane association.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADP-Ribosylation Factors / chemistry*
ADP-Ribosylation Factors / genetics
ADP-Ribosylation Factors / metabolism
Adaptor Proteins, Signal Transducing / chemistry*
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Crystallography, X-Ray
Golgi Apparatus / chemistry
Golgi Apparatus / genetics
Golgi Apparatus / metabolism
Humans
Intracellular Membranes / chemistry
Intracellular Membranes / metabolism
Membrane Proteins / chemistry*
Membrane Proteins / genetics
Membrane Proteins / metabolism
Protein Binding
Protein Multimerization*
Protein Structure, Quaternary
Protein Structure, Tertiary
Structure-Activity Relationship
rac1 GTP-Binding Protein / chemistry
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism

Substances

ARFIP2 protein, human
Adaptor Proteins, Signal Transducing
Membrane Proteins
RAC1 protein, human
ADP-ribosylation factor related proteins
ADP-Ribosylation Factors
rac1 GTP-Binding Protein

Associated data

PDB/4DCN