CRYSTAL STRUCTURE DETERMINATION OF YEAST GET3

酵母 GET3 的晶体结构测定

• 批准号: 8170267
• 负责人: BINGDONG SHA
• 金额: $ 0.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170267
• 关键词: ATP phosphohydrolase; ATP-Binding Cassette Transporters; Adopted; Binding; C-terminal; Complex; Computer Retrieval of Information on Scientific Projects Database; Family; Funding; Golgi Apparatus; Grant; Institution; Integral Membrane Protein; Ligand Binding; Mediating; Membrane; Molecular Conformation; Nucleotides; Pathway interactions; Proteins; Research; Research Personnel; Resources; Signal Recognition Particle; Source; Structure; Tail; Time; Transmembrane Domain; United States National Institutes of Health; Yeasts; 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. Tail-anchored (TA) proteins represent a unique family of transmembrane proteins which contain a single transmembrane helix (about 25 residues) at the C-terminus. The mechanisms how the TA proteins insert the TMD into membranes are distinct from the well-studied co-translational insertion pathway, which is mediated by the cytosolic signal recognition particle (SRP). The post-translational insertion of the TA proteins into ER membrane requires the Golgi ER trafficking (GET) complex which contains Get1, Get2 and Get3. Get3 is an ATPase and can recognize and bind the C- terminal transmembrane domain (TMD) of the TA proteins. It is not well understood how GET complex accomplish the membrane insertion of the TA protein. Recently we have determined the yeast Get3 crystal structure in the open conformation. The structure suggested that Get3 may adopt an open conformation in nucleotide-free state and a closed conformation in ATP-bound state. The conformational changes to switch the Get3 between the open and closed conformations may facilitate the membrane insertions for TA proteins. Get3 may share a similar mechanism as the ABC transporters to transfer bound ligands. Now we are requesting beam time to determine Get3 crystal structure in the closed conformation to confirm our hypothesis.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尾锚定的（TA）蛋白代表了独特的跨膜蛋白家族，该蛋白包含C末端的单个跨膜螺旋（约25个残基）。 TA蛋白如何将TMD插入膜中的机制不同于研究良好的共同插入途径，该插入途径是由胞质信号识别粒子（SRP）介导的。将TA蛋白的翻译后插入到ER膜中需要Golgi ER运输（GET）复合物，其中包含GET1，GET2和GET3。 GET3是ATPase，可以识别和结合TA蛋白的C-末端跨膜结构域（TMD）。尚不清楚如何使复杂完成TA蛋白的膜插入。最近，我们确定了开放构象中的酵母GET3晶体结构。该结构表明，GET3可能在无核苷酸状态下采用开放构象，并在ATP结合状态下采用封闭构象。在开放式和闭合构象之间切换GET3的构象变化可能有助于TA蛋白的膜插入。 GET3可能具有与ABC转运蛋白转移结合配体的类似机制。现在，我们要求光束时间确定封闭构象中的GET3晶体结构，以确认我们的假设。