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-Structure paper
タイトル | Structural insight into an Arl1-ArfGEF complex involved in Golgi recruitment of a GRIP-domain golgin. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 1942, Year 2024 |
掲載日 | 2024年3月2日 |
著者 | H Diessel Duan / Bhawik K Jain / Hua Li / Todd R Graham / Huilin Li / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:38431634 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 4.2 Å |
構造データ | EMDB-28743, PDB-8ezj: EMDB-28744: Cryo-EM consensus map of the S. cerevisiae Arf-like protein Arl1 bound to the Arf guanine nucleotide exchange factor Gea2 EMDB-28746: Cryo-EM local map covering Gea2 protomer B HDS domains of the S. cerevisiae Arf-like protein Arl1 bound to the Arf guanine nucleotide exchange factor Gea2 EMDB-28747: Cryo-EM local map covering Gea2 protomer A HDS domains of the S. cerevisiae Arf-like protein Arl1 bound to the Arf guanine nucleotide exchange factor Gea2 EMDB-28748, PDB-8ezq: EMDB-28749: Cryo-EM consensus map of the S. cerevisiae guanine nucleotide exchange factor Gea2 EMDB-28750: Cryo-EM local map covering Gea2 protomer B HDS domains of the S. cerevisiae guanine nucleotide exchange factor Gea2 EMDB-28751: Cryo-EM local map covering Gea2 protomer A HDS domains of the S. cerevisiae guanine nucleotide exchange factor Gea2 |
化合物 | ChemComp-GTP: |
由来 |
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キーワード | LIPID TRANSPORT / small GTPase / guanine nucleotide exchange factor / membrane trafficking / lipid flippase / trans-Golgi network / protein transport |