一种BRCA1 - BARD1异二聚体RING - RING复合物的结构。

Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.

作者信息

Brzovic P S, Rajagopal P, Hoyt D W, King M C, Klevit R E

机构信息

Department of Biochemistry and Biomolecular Structure Center, University of Washington, Seattle, Washington 98195-7742, USA.

出版信息

Nat Struct Biol. 2001 Oct;8(10):833-7. doi: 10.1038/nsb1001-833.

DOI:10.1038/nsb1001-833

PMID:11573085

Abstract

The RING domain of the breast and ovarian cancer tumor suppressor BRCA1 interacts with multiple cognate proteins, including the RING protein BARD1. Proper function of the BRCA1 RING domain is critical, as evidenced by the many cancer-predisposing mutations found within this domain. We present the solution structure of the heterodimer formed between the RING domains of BRCA1 and BARD1. Comparison with the RING homodimer of the V(D)J recombination-activating protein RAG1 reveals the structural diversity of complexes formed by interactions between different RING domains. The BRCA1-BARD1 structure provides a model for its ubiquitin ligase activity, illustrates how the BRCA1 RING domain can be involved in associations with multiple protein partners and provides a framework for understanding cancer-causing mutations at the molecular level.

摘要

乳腺癌和卵巢癌肿瘤抑制因子BRCA1的环状结构域与多种同源蛋白相互作用，包括环状蛋白BARD1。BRCA1环状结构域的正常功能至关重要，该结构域内发现的许多癌症易感突变就证明了这一点。我们展示了BRCA1和BARD1的环状结构域之间形成的异二聚体的溶液结构。与V(D)J重组激活蛋白RAG1的环状同二聚体比较，揭示了不同环状结构域之间相互作用形成的复合物的结构多样性。BRCA1-BARD1结构为其泛素连接酶活性提供了一个模型，说明了BRCA1环状结构域如何参与与多种蛋白质伙伴的结合，并为在分子水平上理解致癌突变提供了一个框架。