PUBLICATION
Cryo-EM structure of the Mon1-Ccz1-RMC1 complex reveals molecular basis of metazoan RAB7A activation
- Authors
- Yong, X., Jia, G., Liu, Z., Zhou, C., Yi, J., Tang, Y., Chen, L., Chen, L., Wang, Y., Sun, Q., Billadeau, D.D., Su, Z., Jia, D.
- ID
- ZDB-PUB-230523-40
- Date
- 2023
- Source
- Proceedings of the National Academy of Sciences of the United States of America 120: e2301725120e2301725120 (Journal)
- Registered Authors
- Keywords
- Cryo-EM, Rab GTPase, Rab cascade, autophagy, guanine nucleotide exchange factor
- MeSH Terms
-
- Drosophila
- Drosophila Proteins*/ultrastructure
- Animals
- Zebrafish/metabolism
- Cryoelectron Microscopy
- rab GTP-Binding Proteins*/metabolism
- PubMed
- 37216550 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Yong, X., Jia, G., Liu, Z., Zhou, C., Yi, J., Tang, Y., Chen, L., Chen, L., Wang, Y., Sun, Q., Billadeau, D.D., Su, Z., Jia, D. (2023) Cryo-EM structure of the Mon1-Ccz1-RMC1 complex reveals molecular basis of metazoan RAB7A activation. Proceedings of the National Academy of Sciences of the United States of America. 120:e2301725120e2301725120.
Abstract
Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1-Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1-Ccz1-RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the Drosophila Mon1-Ccz1-RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping