Membrane protein biogenesis at the ER

内质网膜蛋白的生物合成

• 批准号: 10406690
• 负责人: Robert J Keenan
• 金额: $ 71.61万
• 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/10406690
• 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.

项目总结/摘要 我的团队试图从分子的细节上了解每一种主要的膜所采取的步骤， 蛋白质达到最终的组装状态。大约四分之一的基因编码膜蛋白 它们首先插入原核生物的质膜或原核生物的内质网（ER）中， 真核生物这些蛋白质执行许多基本功能，如受体、通道、酶、锚定物和 运输机膜蛋白的生物合成是一个固有的效率低下的过程， 疾病与膜蛋白折叠缺陷有关。因此，了解膜蛋白如何 是细胞生物学中的一个基本问题，对人类肿瘤的治疗具有重要意义。 疾病 在人类基因组中编码的约5，000种膜蛋白中，大多数都有一种以上 跨膜结构域然而，我们对这些“多通道”蛋白质如何插入、折叠和 组装成功能实体还处于早期阶段。过去几年在我的小组里的工作使我们 在ER中发现了一种新的~390 kDa的转位子，它参与了大多数多通道的生物发生。 人类细胞中的膜蛋白。我们现在专注于定义潜在的分子机制 这一过程，使用一套跨学科的生物化学，结构，细胞生物学，遗传学和生物信息学 接近。这些研究为膜的基本生物学挑战提供了新的见解 蛋白质生物合成