Molecular contacts in self- assembling clusters of membrane proteins

• 成果类型: Article
• 署名作者: Mandala, Venkata Shiva; Fu, Ziao; Mackinnon, Roderick
• 署名单位: Rockefeller University; Howard Hughes Medical Institute; Rockefeller University; Washington University (WUSTL)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10781
• DOI: 10.1073/pnas.2507112122
• 发表日期: 2025-07-01
• 关键词: hcn channels; k+ channel; kv2.1; DYNAMICS; localization; surface

摘要

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.