Structural and Functional Analysis of the Globular Head Domain of p115 Provides Insight into Membrane Tethering

JOURNAL OF MOLECULAR BIOLOGY

卷:391

Review

An, Yu^1,2  Chen, Christine Y.²  Moyer, Bryan²  Rotkiewicz, Piotr⁴  Elsliger, Marc-Andre¹  Godzik, Adam⁴  Wilson, Ian A.^1,5  Balch, William E.^1,2,3,5,6 

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[4] Burnham Inst Med Res, Program Bioinformat & Syst Biol, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Inst Childhood & Neglected Dis, La Jolla, CA 92037 USA

关键词: vesicle transport;    membrane trafficking;    membrane tethering;    p115;    membrane fusion;   

DOI  :  10.1016/j.jmb.2009.04.062

来源: Elsevier

【 摘 要 】

Molecular tethers have a central role in the organization of the complex membrane architecture of eukaryotic cells. p115 is a ubiquitous, essential tether involved in vesicle transport and the structural organization of the exocytic pathway. We describe two crystal structures of the N-terminal domain of p115 at 2.0 angstrom resolution. The p115 structures show a novel alpha-solenoid architecture constructed of 12 armadillo-like, tether-repeat, alpha-helical tripod motifs. We find that the H1 TR binds the Rab1 GTPase involved in endoplasmic reticulum to Golgi transport. Mutation of the H1 motif results in the dominant negative inhibition of endoplasmic reticulum to Golgi trafficking. We propose that the H1 helical tripod contributes to the assembly of Rab-dependent complexes responsible for the tether and SNARE-dependent fusion of membranes. (c) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free