Analysis BAP-1 as a Ubiquitin Hydrolase in the BRCA1 Pathway
Abstract
The recurrent theme that has emerged from the structural study of proteins is that multiple independently folded globular domain often cooperate in macromolecular recognition. These domains are often recognizable by conserved signature amino acid sequence motifs and their spatial organization within a novel protein is often the first clue to its biochemical function. The PHD finger and bromodomain are two highly conserved protein motifs found in proteins with transcriptional regulatory functions. Optima transcriptional repression by KAP- 1, a universal corepressor for the KRAB-ZFP superfamily of transcriptional repressors, requires an intact PHD finger and bromodomain at its COOH-terminus. Naturally occurring mutations in the PHD finger contribute to a variety of human diseases including cancer. Site-directed mutations in the KAP-1 PHD finger or the bromodomain specifically disrupt the repression function of this bi-partite domain. We have determined a solution structure for the PHD finger of KAP-1. Our studies reveal that the PHD domain binds zinc in a cross-brace topology reminiscent of RING domains.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA388929
Entities
People
- David C. Schultz
Organizations
- University of Pennsylvania