STRUCTURAL STUDIES OF YEAST EXOCYTOSIS

酵母胞吐作用的结构研究

• 批准号: 8169285
• 负责人: AMIR A KHAN
• 金额: $ 0.35万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169285
• 关键词: Binding; Biological; Biological Process; Communicable Diseases; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Eukaryotic Cell; Exocytosis; Family; Funding; Grant; Human; Immune response; Infection; Institution; Interferons; Lead; Light; Mediating; Molecular; Monomeric GTP-Binding Proteins; Natural Immunity; Pathway interactions; Pharmaceutical Preparations; Poxviridae; Property; Proteins; RNA Helicase; Research; Research Personnel; Resources; Signal Transduction; Source; Specificity; Structure; United States National Institutes of Health; Viral; Viral Proteins; Work; X-Ray Crystallography; Yeasts; base; cellular targeting; insight; novel; protein structure; three dimensional structure; trafficking

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. Our lab is investigating the structural basis for cellular signaling using protein X-ray crystallography. One set of projects involve the Rab family of small GTPases, which orchestrate the trafficking of vesicular cargo in eukaryotic cells. Rabs have a conserved three-dimensional fold in their active (GTP) state, yet recognize a distinct subset of effector proteins to mediate their biological effects. Unlike Rabs, effector proteins are diverse in size and composition. We have determined the crystal structures of several Rab-effector complexes to gain insight into specificity and subsequent biological function. The seemingly contradictory properties of specificity and promiscuity - each Rab binds to several unrelated effectors  are being understood in light of emerging structural data. A second set of projects involve the structural basis for poxvirus antagonism of innate immunity. During infection, viral proteins interact with their cellular targets to suppress the immune response and favour viral replication. We have determined the crystal structure of protein K7 in complex with a fragment of its target, human RNA helicase DDX3. The structure reveals the molecular basis for specificity and suggests a mechanism for viral suppression of a key step in the interferon-¿ activation pathway. Similarly, work is continuing toward structural elucidation of other complexes of viral proteins and their cellular targets. Overall, our work in determining the 3-dimensional structures of cellular signaling complexes may lead to the development of novel drugs that modulate key pathways in infectious diseases.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的实验室正在使用蛋白质X射线晶体学研究细胞信号传导的结构基础。 一组项目涉及小GTP酶的Rab家族，其在真核细胞中协调囊泡货物的运输。 Rabs在其活性（GTP）状态下具有保守的三维折叠，但识别效应蛋白的不同子集以介导其生物学效应。 与Rabs不同，效应蛋白在大小和组成上是多样的。 我们已经确定了几个Rab-effector复合物的晶体结构，以深入了解特异性和随后的生物学功能。 特异性和混杂性的看似矛盾的特性-每个Rab与几个不相关的效应物结合  正在根据新出现的结构数据来理解。 第二组项目涉及痘病毒拮抗先天免疫的结构基础。 在感染过程中，病毒蛋白与其细胞靶点相互作用，以抑制免疫反应并促进病毒复制。 我们已经确定了蛋白K7的晶体结构与它的目标，人类RNA解旋酶DDX 3的片段的复合物。 该结构揭示了特异性的分子基础，并提出了干扰素激活途径中关键步骤的病毒抑制机制。 同样，病毒蛋白及其细胞靶点的其他复合物的结构阐明工作仍在继续。 总的来说，我们在确定细胞信号复合物的三维结构方面的工作可能会导致开发调节感染性疾病关键通路的新药。