9RS8

human Fuzzy-Inturned

9RS8 の概要

• エントリーDOI: 10.2210/pdb9rs8/pdb
• EMDBエントリー: 54213
• 分子名称: Protein fuzzy homolog, Protein inturned (2 entities in total)
• 機能のキーワード: longin domain, gef, nucleotide exchange, endosome, autophagosome, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 153215.91

構造登録者

Wilmes, S.,Schaefer, J.,Januliene, D.,Moeller, A.,Kuemmel, D. (登録日: 2025-06-30, 公開日: 2025-07-30, 最終更新日: 2025-09-03)

主引用文献

Wilmes, S.,Tonjes, J.,Drechsler, M.,Ruf, A.,Schafer, J.H.,Lurick, A.,Januliene, D.,Apelt, S.,Di Iorio, D.,Wegner, S.V.,Loose, M.,Moeller, A.,Paululat, A.,Kummel, D.
Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.
Sci Adv, 11:eadx2893-eadx2893, 2025

PubMed Abstract: Rab GTPases organize intracellular trafficking and provide identity to organelles. Their spatiotemporal activation by guanine nucleotide exchange factors (GEFs) is tightly controlled to ensure fidelity. Our structural and functional comparison of the tri-longin domain RabGEFs Mon1-Ccz1 and Fuzzy-Inturned reveals the molecular basis for their target specificity. Both complexes rely on a conserved sequence motif of their substrate GTPases for the catalytic mechanism, while secondary interactions allow discrimination between targets. We also find that dimeric Mon1-Ccz1 from fungi and the metazoan homologs with the additional third subunit RMC1/Bulli bind membranes through electrostatic interactions via distinct interfaces. Protein-lipid interaction studies and functional characterization in flies reveal an essential function of RMC1/Bulli as mediator of GEF complex membrane recruitment. In the case of Fuzzy-Inturned, reconstitution experiments demonstrate that the BAR (Bin-Amphiphysin-Rvs) domain protein CiBAR1 can support membrane recruitment of the GEF. Collectively, our study demonstrates the molecular basis for the adaptation of TLD-RabGEFs to different cellular functions.

PubMed: 40864718
DOI: 10.1126/sciadv.adx2893

実験手法

ELECTRON MICROSCOPY (3.7 Å)