8EZQ

Cryo-EM structure of the S. cerevisiae guanine nucleotide exchange factor Gea2

8EZQ の概要

• エントリーDOI: 10.2210/pdb8ezq/pdb
• EMDBエントリー: 28748
• 分子名称: ARF guanine-nucleotide exchange factor 2 (1 entity in total)
• 機能のキーワード: small gtpase, guanine nucleotide exchange factor, membrane trafficking, lipid flippase, trans-golgi network, protein transport, lipid transport
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 337181.41

構造登録者

Duan, H.D.,Li, H. (登録日: 2022-11-01, 公開日: 2023-11-15, 最終更新日: 2024-03-13)

主引用文献

Duan, H.D.,Jain, B.K.,Li, H.,Graham, T.R.,Li, H.
Structural insight into an Arl1-ArfGEF complex involved in Golgi recruitment of a GRIP-domain golgin.
Nat Commun, 15:1942-1942, 2024

PubMed Abstract: Arl1 is an Arf-like (Arl) GTP-binding protein that interacts with the guanine nucleotide exchange factor Gea2 to recruit the golgin Imh1 to the Golgi. The Arl1-Gea2 complex also binds and activates the phosphatidylserine flippase Drs2 and these functions may be related, although the underlying molecular mechanism is unclear. Here we report high-resolution cryo-EM structures of the full-length Gea2 and the Arl1-Gea2 complex. Gea2 is a large protein with 1459 residues and is composed of six domains (DCB, HUS, SEC7, HDS1-3). We show that Gea2 assembles a stable dimer via an extensive interface involving hydrophobic and electrostatic interactions in the DCB and HUS region. Contrary to the previous report on a Gea2 homolog in which Arl1 binds to the dimerization surface of the DCB domain, implying a disrupted dimer upon Arl1 binding, we find that Arl1 binds to the outside surface of the Gea2 DCB domain, leaving the Gea2 dimer intact. The interaction between Arl1 and Gea2 involves the classic FWY aromatic residue triad as well as two Arl1-specific residues. We show that key mutations that disrupt the Arl1-Gea2 interaction abrogate Imh1 Golgi association. This work clarifies the Arl1-Gea2 interaction and improves our understanding of molecular events in the membrane trafficking.

PubMed: 38431634
DOI: 10.1038/s41467-024-46304-w

実験手法

ELECTRON MICROSCOPY (3.7 Å)