MOLECULAR CHARACTERIZATION OF GLUCOSE TRANSPORTERS

葡萄糖转运蛋白的分子表征

• 批准号: 2443900
• 负责人: CHAN Y. JUNG
• 金额: $ 13.1万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2443900
• 关键词: affinity labeling; chemical binding; chemical models; chemical structure function; crosslink; crystallization; diabetes mellitus; glucose transporter; high performance liquid chromatography; hormone regulation /control mechanism; human tissue; insulin sensitivity /resistance; laboratory rat; mass spectrometry; membrane proteins; molecular cloning; molecular pathology; monocyte; obesity; protein sequence; protein structure function; transport proteins

Glucose uptake and release by mammalian cells is a tightly controlled process, mediated by a family of intrinsic membrane proteins (facilitative glucose transporters) and subjected to hormonal and metabolic regulation, whose dysfunction may produce insulin-resistance seen in diabetes and obesity. The long term goal of this proposal is to identify the nature of the transporter defects underlying these diseases. More immediate goals are to determine the detailed protein structure to understand how it translocates glucose and how it is regulated by metabolites and hormones. Specifically, we propose and will test a discrete molecular model for the transmembrane helices (TMHs) structure of GLUT1, a member of this protein family. We will identify those TMH amino acid residues (i) that line putative glucose channel by covalently labeling them with transportable glucose analogs, (ii) that involved in transmembrane helix packing by chemical crosslinking and by site-directed pyrene labeling of paired Cys replacement mutants, and (iii) that interface with the lipid bilayer using lipophilic probes. We will also try to grow protein crystals suitable for X-ray and/or electron diffraction studies.

哺乳动物细胞对葡萄糖的摄取和释放受到严格控制