STRUCUTRAL STUDIES OF THE KAR3-VIK1, KAR3-CIK1 HETERODIMER MOTOR PROTEINS

KAR3-VIK1、KAR3-CIK1 异二聚体运动蛋白的结构研究

• 批准号: 8361236
• 负责人: IVAN RAYMENT
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361236
• 关键词: Binding; Communication; Exhibits; Funding; Grant; Kinesin; Microtubules; Molecular; Molecular Motors; Motor; Movement; National Center for Research Resources; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; base; cost; insight; member

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This research focuses on the molecular mechanism for Kar3 which belongs to the Kinesin-14 class of motors. Members of the Kinesin-14 motors are minus-end directed, non processive kinesins that operate with a powerstroke mechanism. Kar3 represents a unique opportunity to study the common functional asymmetry in non processive multimeric kinesins, including homodimeric examples such as Ncd, as Kar3 functions as a heterodimer with either Vik1 or Cik1. Vik1 and Cik1 are not molecular motors, yet we have recently shown that Vik1 contains a globular domain that exhibits the same fold as the kinesin motor domain. This domain binds more tightly to microtubules than Kar3, but does not hydrolyze ATP. This demands the existence of intermolecular communication between the motor and non motor domains in order to generate movement. Based on sequence similarity, Cik1 is predicted to contain a motor homology domain. Thus, Katherine's research should provide valuable insight into the common functional asymmetry that manifests itself in non processive molecular motors. NMR will be used to synthesize a high capacity strep column which will aid in the purification of Kar3-Vik1 and Kar3-Cik1 heterodimers.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究的重点是Kar 3的分子机制，它属于驱动蛋白-14类马达。 驱动蛋白-14马达的成员是负端定向的，非进行性驱动蛋白，其与动力冲程机制一起操作。 Kar 3代表了一个独特的机会，研究非进行性多聚体驱动蛋白中常见的功能不对称性，包括同源二聚体的例子，如Ncd，因为Kar 3作为异源二聚体与Vik 1或Cik 1一起发挥作用。 Vik 1和Cik 1不是分子马达，但我们最近发现Vik 1包含一个球状结构域，该结构域与驱动蛋白马达结构域具有相同的折叠。 该结构域比Kar 3更紧密地结合微管，但不水解ATP。 这就要求运动域和非运动域之间存在分子间通讯，以产生运动。 基于序列相似性，预测Cik 1含有马达同源结构域。 因此，凯瑟琳的研究应该提供有价值的洞察力，以共同的功能不对称，表现在非加工分子马达本身。 NMR将用于合成高容量strep柱，其将有助于Kar 3-Vik 1和Kar 3-Cik 1异二聚体的纯化。