GTP-BINDING PROTEINS AND SIGNAL TRANSDUCTION--STRUCTURE AND FUNCTION

GTP 结合蛋白和信号转导——结构和功能

• 批准号: 3841161
• 负责人: M RODBELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841161
• 关键词: G protein; biological signal transduction; crosslink; detergents; guanosine triphosphate; maleimides; nucleotide analog; polymers; protein structure function; receptor coupling; synaptosomes

Previous studies established that GTP-binding regulatory proteins (G- proteins) can be extracted from hepatic and brain membranes with octyglucoside as large structures (>12S) suggestive of multimers. Exposure of these membranes to activating guanine nucleotide (GTPgammaS) alone or with hormone (glucagon, with liver) caused the large structures to break down into structures similar is size to heterotrimeric G-proteins. Several types of G-proteins were shown to have different size multimers depending on the type of detergent used for extraction; each G-protein type displayed distinct sensitivity to the "depolymerizing" actions of GTPgammaS. Synaptoneurosome membranes treated with p-phenylenedimaleimide were shown to contain cross-linked G-proteins that, on sizing columns, resemble the polymeric forms of actin and tubulin in these membranes. These findings coupled with the detergent studies and target size analysis of adenylyl cyclase systems suggest that membrane receptors are linked to multimeric structures of G-proteins. A new concept of hormone action is proposed which takes into account the multimeric structures of G-proteins and which suggests that the coupling and dynamics of receptor/G-protein interactions are controlled by the binding and hydrolysis of GTP, analogous to the ATPase-controlled interactions of multimeric actin and myosin.

先前的研究证实gtp结合调节蛋白(G-