Insights into the distinct membrane targeting mechanisms of WDR91 family proteins.

Publication Type:

Journal Article

Authors:

Ma, Xinli; Li, Jian; Liu, Nan; Banerjee, Surajit; Hu, Xiaotong; Wang, Xiaoyu; Dong, Jianshu; Liu, Kangdong; Yang, Chonglin; Dong, Zigang

Source:

Structure, Volume 32, Issue 12, p.2287-2300.e4 (2024)

Keywords:

Amino Acid Sequence, Binding Sites, Carrier Proteins, Crystallography, X-Ray, Endosomes, HEK293 Cells, Humans, Models, Molecular, Protein Binding, Protein Transport, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins, WD40 Repeats

Abstract:

<p>WDR91 and SORF1, members of the WD repeat-containing protein 91 family, control phosphoinositide conversion by inhibiting phosphatidylinositol 3-kinase activity on endosomes, which promotes endosome maturation. Here, we report the crystal structure of the human WDR91 WD40 domain complexed with Rab7 that has an unusual interface at the C-terminus of the Rab7 switch II region. WDR91 is highly selective for Rab7 among the tested GTPases. A LIS1 homology (LisH) motif within the WDR91 N-terminal domain (NTD) mediates self-association and may contribute partly to the augmented interaction between full-length WDR91 and Rab7. Both the Rab7 binding site and the LisH motif are indispensable for WDR91 function in endocytic trafficking. For the WDR91 orthologue SORF1 lacking the C-terminal WD40 domain, a C-terminal amphipathic helix (AH) mediates strong interactions with liposomes containing acidic lipids. During evolution the human WDR91 ancestor gene might have acquired a WD40 domain to replace the AH for endosomal membrane targeting.</p>

PDB: 
8KB9, 8KB8
Detector: 
PILATUS
Beamline: 
24-ID-C