Title | Structural basis for the histone chaperone activity of Asf1. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | English CM, Adkins MW, Carson JJ, Churchill MEA, Tyler JK |
Journal | Cell |
Volume | 127 |
Issue | 3 |
Pagination | 495-508 |
Date Published | 2006 Nov 03 |
ISSN | 0092-8674 |
Keywords | Amino Acid Substitution, Cell Cycle Proteins, Chromatin, Crystallography, X-Ray, Dimerization, Gene Silencing, Histones, Models, Molecular, Molecular Chaperones, Nucleosomes, Protein Conformation, Protein Structure, Secondary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins |
Abstract | Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. The structure of the globular domain of Asf1 bound to H3/H4 determined by X-ray crystallography to a resolution of 1.7 Angstroms shows how Asf1 binds the H3/H4 heterodimer, enveloping the C terminus of histone H3 and physically blocking formation of the H3/H4 heterotetramer. Unexpectedly, the C terminus of histone H4 that forms a mini-beta sheet with histone H2A in the nucleosome undergoes a major conformational change upon binding to Asf1 and adds a beta strand to the Asf1 beta sheet sandwich. Interactions with both H3 and H4 were required for Asf1 histone chaperone function in vivo and in vitro. The Asf1-H3/H4 structure suggests a "strand-capture" mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly/assembly that may be used ubiquitously by histone chaperones. |
DOI | 10.1016/j.cell.2006.08.047 |
Alternate Journal | Cell |
PubMed ID | 17081973 |
PubMed Central ID | PMC2981792 |
Grant List | GM064475 / GM / NIGMS NIH HHS / United States R01 CA095641 / CA / NCI NIH HHS / United States R01 GM064475 / GM / NIGMS NIH HHS / United States R01 GM079154 / GM / NIGMS NIH HHS / United States R01 GM079154-01A1 / GM / NIGMS NIH HHS / United States |
Related Lab:
Related Faculty:
Jessica K. Tyler, Ph.D.