Higher- order transient membrane protein structures

• 成果类型: Article
• 署名作者: Zhang, Yuxi; Mazal, Hisham; Mandala, Venkata Shiva; Perez-Mitta, Gonzalo; Sondoghdar, Vahid; Haselwandter, Christoph A.; Mackinnon, Roderick
• 署名单位: Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; Max Planck Society; University of Erlangen Nuremberg; University of Southern California; University of Southern California
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11916
• DOI: 10.1073/pnas.2421275121
• 发表日期: 2024-01-07
• 关键词: plasma-membrane; muscarinic receptors; DYNAMICS; distinct; activation; adenosine; clusters; channels; cells

摘要

This study shows that five membrane proteins-three GPCRs, an ion channel, and an enzyme-form self- clusters under natural expression levels in a cardiac- derived cell line. The cluster size distributions imply that these proteins self- oligomerize reversibly through weak interactions. When the concentration of the proteins is increased through heterologous expression, the cluster size distributions approach a critical distribution at which point a phase transition occurs, yielding larger bulk phase clusters. A thermodynamic model like that explaining micellization of amphiphiles and lipid membrane formation accounts for this behavior. We propose that many membrane proteins exist as oligomers that form through weak interactions, which we call higher- order transient structures (HOTS). The key characteristics of HOTS are transience, molecular specificity, and a monotonically decreasing size distribution that may become critical at high concentrations. Because molecular specificity invokes self- recognition through protein sequence and structure, we propose that HOTS are genetically encoded supramolecular units.