Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.

ABSTRACT: Autophagy is a fundamental cellular process, conserved across species from yeast to mammals, that plays a crucial role in maintaining cellular homeostasis. The functionally conserved MON1-CCZ1 (MC1) complex serves as a guanine nucleotide exchange factor (GEF) for the RAB GTPase RAB7A and is indispensable for directing RAB7A recruitment to autophagosome or lysosomal membranes. Despite its critical role, the precise molecular mechanism underlying the assembly of the human MON1A-CCZ1 (HsMC1) complex and its specific GEF activity towards RAB7A has remained unclear. In this study, we report the high-resolution cryo-electron microscopy (cryo-EM) structure of the HsMC1 GEF domain in a complex with the nucleotide-free RAB7A^N125I at 2.85 Å resolution. Our structural data demonstrate that

SUBMITTER: Li X 

PROVIDER: S-EPMC12448474 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature