TM INTERACTIONS IN MEMBRANE PROTEIN FOLDING AND FUNCTION

膜蛋白折叠和功能中的 TM 相互作用

• 批准号: 7233213
• 负责人: DONALD M. ENGELMAN
• 金额: $ 37.83万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233213
• 关键词: Affect; Algorithms; Amino Acids; Architecture; Area; Biochemical Genetics; Biological; Biological Assay; Biological Process; Chemistry; Classification; Code; Collaborations; Computer Simulation; Computing Methodologies; Dimerization; Fluorescence Resonance Energy Transfer; Gene Targeting; Genetic Screening; HIV Envelope Protein gp41; Helix (Snails); In Vitro; Informatics; Label; Laboratories; Lead; Link; Lipids; Major Histocompatibility Complex; Membrane; Membrane Proteins; Methods; Micelles; Modeling; Mutation; NMR Spectroscopy; Nature; Numbers; Object Attachment; Optics; Pharmaceutical Preparations; Protein Tyrosine Phosphatase; Rest; Rewards; Role; Signal Transduction; Solvents; Specific qualifier value; Structure; Surface; Tertiary Protein Structure; Testing; Water; Work; analytical ultracentrifugation; dimer; ear helix; glycylproline; improved; next generation; programs; protein folding; protein structure; receptor; simulation

DESCRIPTION (provided by applicant): Interactions between transmembrane helices are a major feature of the architecture of membrane proteins. Understanding the principles that guide such interactions will illuminate membrane protein folding, stability, and oligomer formation. Since membrane proteins are coded by more than 20% of all genes and are the targets of more than half of all drugs, such an understanding will be both enlightening and useful. We will work towards understanding the motifs and interactions that give rise to transmembrane helix (TM) interactions that stabilize protein structures in biological membranes, and to begin to connect our understanding to biological functions. We have developed a diverse toolkit for the study of TM interactions, including: (a) genetic and biochemical assays in micelles, bilayers and membranes, (b) computational approaches, and (c) structural studies using optical spectroscopy and NMR. Our approach will have several major divisions: a study of TM trimers in HIV gp41 TMs and MHC li; an effort to find the link between helix dimerization and signaling; a study of interaction motifs; an improvement of TM-TM computational methods; and tests of the principles and motifs that can be identified in helix associations.

描述（由申请人提供）：跨膜螺旋之间的相互作用是膜蛋白结构的主要特征。了解指导这种相互作用的原理将阐明膜蛋白折叠、稳定性和寡聚体的形成。由于膜蛋白是由超过 20% 的基因编码的，并且是超过一半药物的靶标，因此这种理解既具有启发性又很有用。我们将努力了解引起跨膜螺旋（TM）相互作用的基序和相互作用，从而稳定生物膜中的蛋白质结构，并开始将我们的理解与生物功能联系起来。我们开发了用于研究 TM 相互作用的多样化工具包，包括：(a) 胶束、双层和膜中的遗传和生化测定，(b) 计算方法，以及 (c) 使用光谱和核磁共振的结构研究。我们的方法将分为几个主要部分：HIV gp41 TM 和 MHC li 中 TM 三聚体的研究；努力寻找螺旋二聚化和信号传导之间的联系；交互主题的研究； TM-TM计算方法的改进；以及可在螺旋关联中识别的原理和基序的测试。