MOLECULAR ARCHITECTURES OF BTB-CUL3 UBIQUITIN LIGASES

BTB-CUL3 泛素连接酶的分子结构

• 批准号: 8169289
• 负责人: BRENDA A SCHULMAN
• 金额: $ 0.52万
• 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/8169289
• 关键词: Architecture; BTB/POZ Domain; Binding; Boxing; C-terminal; Catalytic Domain; Complex; Computer Retrieval of Information on Scientific Projects Database; Dimerization; F Box Domain; F-Box Motifs; F-Box Proteins; Funding; Genome; Grant; Human Genome; Institution; Link; Molecular; Property; Proteins; Recruitment Activity; Research; Research Personnel; Resources; SKP Cullin F-Box Protein Ligases; Source; Ubiquitination; United States National Institutes of Health; in vivo; member; polypeptide; protein complex; ubiquitin ligase; ubiquitin-protein ligase

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. The best understood Cullin-RING E3 ubiquitin ligase (CRL) is the SCF ubiquitin ligase, composed of Cul1, Skp1 and a member of the F-box family of proteins. Skp1 serves as an adaptor that simultaneously binds sequences near the N-terminus of Cul1 and the F-box motif of an F-box protein. In turn, F-box proteins contain additional protein interaction domains that recruit the substrate into a Cul1-Skp1-F-box protein complex, thereby facilitating ubiquitination of the target via the catalytic core assembled on the C-terminus of Cul1. In contrast, Cul3 employs BTB proteins as substrate specific adaptor. "BTB" is a protein interaction/dimerization domain that is structurally homologous to the cullin-binding region of Skp1, and that binds Cul3 via motifs analogous to those in the Skp1-Cul1 complex. Many BTB-domain proteins also contain additional protein interaction domains, some of which have been shown to recruit ubiquitination targets. Thus, BTB proteins are thought to merge the functional properties of Skp1or EloC and their F-box or SOCS-box partners into a single polypeptide chain, without an intervening F- or SOCS- box. The human genome encodes more than 150 proteins with recognizable BTB domains, often in combination with MATH, Kelch, or other interaction domains. BTB proteins containing MATH and Kelch domains have been linked to substrate targeting by Cul3, although it is unclear precisely how many BTB proteins engage Cul3 in vivo. Also, little is known about how MATH domains select targets for ubiquitination by CRLs. The MATH domain, present in numerous diverse proteins, is most frequently found linked to a C-terminal BTB domain. Indeed, the MATH-BTB module is the 10th most abundant of 2-domain combinations encoded by 131 genomes.

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。 Cullin-RING E3泛素连接酶（CRL）是SCF泛素连接酶，由Cul 1、Skp 1和F-box蛋白家族成员组成。Skp 1作为一个衔接子，同时结合Cul 1的N-末端附近的序列和F-box蛋白的F-box基序。反过来，F-box蛋白含有额外的蛋白质相互作用结构域，其将底物募集到Cul 1-Skp 1-F-box蛋白复合物中，从而通过组装在Cul 1的C-末端上的催化核心促进靶标的泛素化。相反，Cul 3采用BTB蛋白作为底物特异性衔接子。“BTB”是一种蛋白质相互作用/二聚化结构域，其在结构上与Skp 1的cullin结合区同源，并通过与Skp 1-Cul 1复合物中的基序类似的基序结合Cul 3。许多BTB结构域蛋白还含有额外的蛋白质相互作用结构域，其中一些已被证明可以招募泛素化靶点。因此，BTB蛋白被认为将Skp 1或EloC及其F盒或SOCS盒配偶体的功能特性合并到单个多肽链中，而没有插入的F盒或SOCS盒。 人类基因组编码超过150种具有可识别的BTB结构域的蛋白质，通常与MATH，Kelch或其他相互作用结构域组合。 含有MATH和Kelch结构域的BTB蛋白已经与Cul 3的底物靶向相关联，尽管目前还不清楚确切地有多少BTB蛋白在体内与Cul 3接合。 此外，关于MATH结构域如何通过CRL选择泛素化的目标知之甚少。MATH结构域存在于许多不同的蛋白质中，最常发现与C-末端BTB结构域连接。事实上，MATH-BTB模块是由131个基因组编码的第10个最丰富的2结构域组合。