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.

项目概要/摘要 我的小组试图从分子细节上了解每一类主要的膜所采取的步骤 大约四分之一的基因编码膜蛋白。 首先插入原核生物的质膜或内质网（ER） 这些蛋白质执行许多重要的功能，如受体、通道、酶、锚和 膜蛋白的生物合成本质上是一个低效的过程，并且许多人类 疾病与膜蛋白折叠缺陷有关。因此，了解膜蛋白如何折叠。 是细胞生物学中的一个基本问题，对人类的治疗具有重要意义 疾病。 在人类基因组编码的约 5,000 种膜蛋白中，大多数都具有不止一种 然而我们对这些“多次”蛋白质如何插入、折叠和的理解。 组装成功能实体尚处于早期阶段，过去几年我们团队的工作使我们实现了这一目标。 在 ER 中发现一种新的约 390 kDa 易位子，该易位子参与大多数多通道的生物发生 我们现在专注于定义人类细胞中的膜蛋白。 这个过程使用了一系列跨学科的生物化学、结构、细胞生物学、遗传和生物信息学 这些研究为膜的基本生物学挑战提供了新的见解。 蛋白质生物发生。