MODELING THE STRUCTURE OF A RECEPTOR WITH TWO ASSOCIATING TRANSMEMBRANE DOMAINS

对具有两个相关跨膜域的受体结构进行建模

• 批准号: 7957685
• 负责人: DAVID BAKER
• 金额: $ 3.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957685
• 关键词: Biology; Cell surface; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Computing Methodologies; Cytoplasmic Tail; Dissociation; Funding; Fungal Genome; Glycophorin A; Grant; Homo; Institution; Integrins; Joints; Length; Membrane; Modeling; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Structure; Transmembrane Domain; United States National Institutes of Health; dimer; extracellular; flexibility; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structures of intact receptors with single-pass transmembrane domains are essential to understand how extracellular and cytoplasmic domains regulate association and signaling through transmembrane domains. A chemical and computational method to determine structures of the membrane regions of such receptors on the cell surface is developed here and validated with glycophorin A. An integrin heterodimer structure reveals association over most of the lengths of the alpha and beta transmembrane domains and shows that the principles governing association of hetero and homo transmembrane dimers differ. A turn at the Gly of the juxtamembrane GFFKR motif caps the alpha TM helix and brings the two Phe of GFFKR into the alpha/beta interface. A juxtamembrane Lys residue in beta also has an important role in the interface. The structure shows how transmembrane association/dissociation regulates integrin signaling. A joint ectodomain and membrane structure shows that substantial flexibility between the extracellular and TM domains is compatible with TM signaling.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具有单次通过跨膜区的完整受体的结构对于了解胞外和胞内区如何通过跨膜区调节关联和信号是至关重要的。建立了一种化学和计算方法来确定细胞表面这类受体的膜区域的结构，并用血糖素A进行了验证。整合素异二聚体的结构揭示了α和β跨膜结构域的大部分长度上的结合，并表明异质和同质跨膜二聚体的结合原理不同。GFFKR基序的Gly处的一个转弯封顶了GFFKR的αTM螺旋，并将GFFKR的两个Phe带入了α/β界面。膜旁的赖氨酸残基在界面上也起着重要作用。该结构显示了跨膜结合/解离如何调节整合素信号。胞外结构域和膜结构的结合表明，胞外结构域和TM结构域之间的相当大的灵活性与TM信号是相容的。