Journal article
Molecular contacts in self-assembling clusters of membrane proteins
Proceedings of the National Academy of Sciences - PNAS, Vol.122(26), p.e2507112122
07/01/2025
DOI: 10.1073/pnas.2507112122
PMCID: PMC12232663
PMID: 40549920
Abstract
Many proteins function not just in isolation but also by interacting with other proteins as part of signaling pathways in living cells. Much is already known about the structures of different proteins and what role they play in organisms. But molecular details of how different proteins interact with each other to form larger assemblies are not well understood. Here, we study how several different membrane proteins self-interact to form clusters. We find that proteins contact each other in a variety of ways—involving both ordered and disordered regions—to form these self-clusters, highlighting the diversity of chemical interactions nature uses in the formation of protein assemblies in cell membranes. Motivated by recent data pointing to the existence of homo-oligomeric assemblies of membrane proteins called higher-order transient structures, and their apparent role in connecting components of membrane signal pathways, we examine here by cryoelectron microscopy some of the protein–protein interactions that occur in cluster formation. Metabotropic glutamate receptors and HCN ion channels inside clusters contact their neighbors through structured extracellular and intracellular domains, respectively. Other ion channels, including Kv2.1 and Slo1, appear to form clusters through prominent intrinsically disordered sequences in the cytoplasm. These distinct modes of interaction are associated with clusters exhibiting varying degrees of compactness and order. We conclude that nature utilizes a variety of ways to form connections between membrane proteins in self-assembled clusters.
Details
- Title: Subtitle
- Molecular contacts in self-assembling clusters of membrane proteins
- Creators
- Venkata Shiva Mandala - Rockefeller UniversityZiao Fu - Rockefeller UniversityRoderick MacKinnon - Rockefeller University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.122(26), p.e2507112122
- DOI
- 10.1073/pnas.2507112122
- PMID
- 40549920
- PMCID
- PMC12232663
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Grant note
- NA / ; 61-1781 / ;
- Language
- English
- Date published
- 07/01/2025
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985113009502771
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