TY - JOUR
T1 - Structure of the coiled-coil dimerization motif of Sir4 and its interaction with Sir3
AU - Chang, Ju Fang
AU - Hall, Brian E.
AU - Tanny, Jason C.
AU - Moazed, Danesh
AU - Filman, David
AU - Ellenberger, Tom
N1 - Funding Information:
We thank Stephen Blacklow, Peggy C. Stolt, and Patrick O'Brien for advice and assistance with circular dichroism measurements and Henry Ho for assistance with centrifugation studies. We also thank Eric Toth, Laura Silvian, Tom Hollis, Brandt Eichman, Masato Kato, and the staff of the macromolecular crystallography resource at the National Synchrotron Light Source (Upton, NY) for help with X-ray data collection and analysis. This work was supported by grants from the National Institutes of Health (R01 GM52506 to T.E. and R01 GM61641 to D.M.) and the resources of the Harvard-Armenise Structural Biology Center. T.E. is grateful for the support of the Hsien Wu and Daisy Yen Wu Professorship at Harvard Medical School.
PY - 2003/6
Y1 - 2003/6
N2 - The yeast silent information regulators Sir2, Sir3, and Sir4 physically interact with one another to establish a transcriptionally silent state by forming repressive chromatin structures. The Sir4 protein contains binding sites for both Sir2 and Sir3, and these protein-protein interactions are required for gene silencing. Here, we report the X-ray structure of the coiled-coil dimerization motif within the C-terminus of Sir4 and show that it forms a stable 1:1 complex with a dimeric fragment of Sir3 (residues 464-978). We have identified a cluster of residues on the surface of the Sir4 coiled coil required for specific interactions with Sir3. The histone deacetylase Sir2 can also bind to this complex, forming a ternary complex with the truncated Sir3 and Sir4 proteins. The dual interactions of Sir4 with Sir3 and Sir2 suggest a physical basis for recruiting Sir3 to chromatin by virtue of its interactions with Sir4 and with deacetylated histones in chromatin.
AB - The yeast silent information regulators Sir2, Sir3, and Sir4 physically interact with one another to establish a transcriptionally silent state by forming repressive chromatin structures. The Sir4 protein contains binding sites for both Sir2 and Sir3, and these protein-protein interactions are required for gene silencing. Here, we report the X-ray structure of the coiled-coil dimerization motif within the C-terminus of Sir4 and show that it forms a stable 1:1 complex with a dimeric fragment of Sir3 (residues 464-978). We have identified a cluster of residues on the surface of the Sir4 coiled coil required for specific interactions with Sir3. The histone deacetylase Sir2 can also bind to this complex, forming a ternary complex with the truncated Sir3 and Sir4 proteins. The dual interactions of Sir4 with Sir3 and Sir2 suggest a physical basis for recruiting Sir3 to chromatin by virtue of its interactions with Sir4 and with deacetylated histones in chromatin.
UR - http://www.scopus.com/inward/record.url?scp=0142134870&partnerID=8YFLogxK
U2 - 10.1016/S0969-2126(03)00093-5
DO - 10.1016/S0969-2126(03)00093-5
M3 - Article
C2 - 12791253
AN - SCOPUS:0142134870
SN - 0969-2126
VL - 11
SP - 637
EP - 649
JO - Structure
JF - Structure
IS - 6
ER -