Membrane protein biogenesis at the ER

内质网膜蛋白的生物发生

• 批准号: 10652499
• 负责人: Robert J Keenan
• 金额: $ 68.33万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652499
• 关键词: Anabolism; Biochemical; Biogenesis; Bioinformatics; Biological; Cell membrane; Cell physiology; Cells; Cellular biology; Code; Endoplasmic Reticulum; Enzymes; Eukaryota; Eukaryotic Cell; Genes; Genetic; Growth; Human; Human Genome; Link; Membrane; Membrane Proteins; Molecular; Pathway interactions; Process; Prokaryotic Cells; Proteins; Transmembrane Domain; Work; human disease; insight; novel; receptor

PROJECT SUMMARY/ABSTRACT My group seeks to understand, in molecular detail, the steps taken by each of the major classes of membrane proteins to achieve their final assembled state. About one-quarter of all genes code for membrane proteins that are first inserted into the plasma membrane of prokaryotes or the endoplasmic reticulum (ER) of eukaryotes. These proteins perform many essential functions as receptors, channels, enzymes, anchors and transporters. Biosynthesis of membrane proteins is an inherently inefficient process, and numerous human diseases are linked to defective folding of membrane proteins. Thus, understanding how membrane proteins are made is a fundamental question in cell biology with important implications for the treatment of human diseases. Of the ~5,000 membrane proteins coded in the human genome, the majority have more than one transmembrane domain. Yet our understanding of how these “multi-pass” proteins are inserted, folded and assembled into functional entities is at an early stage. Work in my group over the past several years led us to discover a novel ~390 kDa translocon in the ER that is involved in the biogenesis of most multi-pass membrane proteins in human cells. We are now focused on defining the molecular mechanisms underlying this process, using an interdisciplinary set of biochemical, structural, cell biological, genetic and bioinformatic approaches. These studies promise new insight into the fundamental biological challenge of membrane protein biogenesis.

项目摘要/摘要 我的小组试图从分子细节中理解每个主要类别的膜所采取的步骤 蛋白质以达到最终组装状态。大约四分之一的膜蛋白基因代码 首先插入原核生物的质膜或内质网（ER） 真核生物。这些蛋白质作为接收器，通道，酶，锚和 运输商。膜蛋白的生物合成是一种固有的无效过程，许多人 疾病与膜蛋白的折叠有缺陷有关。了解膜蛋白如何 制作是细胞生物学中的一个基本问题，对人类的治疗有重要影响 疾病。 在人类基因组中编码的约5,000个膜蛋白中，大多数有多个 跨膜结构域。然而，我们对这些“多通”蛋白如何插入，折叠和 组装成功能实体是在早期阶段。在过去的几年中，我小组的工作使我们 在ER中发现一个新颖的〜390 kDa转运，该易生生物发生 人类细胞中的膜蛋白。现在，我们专注于定义下面的分子机制 此过程，使用跨学科的生化，结构，细胞生物学，遗传学和生物信息学 方法。这些研究有望对膜的基本生物学挑战进行新的见解 蛋白质生物发生。