The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module

@article{citeulike:2946182, abstract = {The FACT complex is a conserved cofactor for RNA polymerase II elongation through nucleosomes. FACT bears histone chaperone activity and contributes to chromatin integrity. However, the molecular mechanisms behind FACT function remain elusive. Here we report biochemical, structural, and mutational analyses that identify the peptidase homology domain of the Schizosaccharomyces pombe FACT large subunit Spt16 (Spt16-N) as a binding module for histones H3 and H4. The 2.1-A crystal structure of Spt16-N reveals an aminopeptidase P fold whose enzymatic activity has been lost. Instead, the highly conserved fold directly binds histones H3-H4 through a tight interaction with their globular core domains, as well as with their N-terminal tails. Mutations within a conserved surface pocket in Spt16-N or posttranslational modification of the histone H4 tail reduce interaction in vitro, whereas the globular domains of H3-H4 and the H3 tail bind distinct Spt16-N surfaces. Our analysis suggests that the N-terminal domain of Spt16 may add to the known H2A-H2B chaperone activity of FACT by including a H3-H4 tail and H3-H4 core binding function mediated by the N terminus of Spt16. We suggest that these interactions may aid FACT-mediated nucleosome reorganization events. 10.1073/pnas.0712293105}, author = {Stuwe, Tobias and Hothorn, Michael and Lejeune, Erwan and Rybin, Vladimir and Bortfeld, Miriam and Scheffzek, Klaus and Ladurner, Andreas G. }, citeulike-article-id = {2946182}, doi = {http://dx.doi.org/10.1073/pnas.0712293105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {fact, spt16}, month = {June}, pages = {0712293105+}, posted-at = {2008-07-01 02:13:08}, priority = {2}, title = {The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module}, url = {http://dx.doi.org/10.1073/pnas.0712293105}, year = {2008} }

TY - JOUR ID - citeulike:2946182 L3 - citeulike-article-id:2946182 N2 - The FACT complex is a conserved cofactor for RNA polymerase II elongation through nucleosomes. FACT bears histone chaperone activity and contributes to chromatin integrity. However, the molecular mechanisms behind FACT function remain elusive. Here we report biochemical, structural, and mutational analyses that identify the peptidase homology domain of the Schizosaccharomyces pombe FACT large subunit Spt16 (Spt16-N) as a binding module for histones H3 and H4. The 2.1-A crystal structure of Spt16-N reveals an aminopeptidase P fold whose enzymatic activity has been lost. Instead, the highly conserved fold directly binds histones H3-H4 through a tight interaction with their globular core domains, as well as with their N-terminal tails. Mutations within a conserved surface pocket in Spt16-N or posttranslational modification of the histone H4 tail reduce interaction in vitro, whereas the globular domains of H3-H4 and the H3 tail bind distinct Spt16-N surfaces. Our analysis suggests that the N-terminal domain of Spt16 may add to the known H2A-H2B chaperone activity of FACT by including a H3-H4 tail and H3-H4 core binding function mediated by the N terminus of Spt16. We suggest that these interactions may aid FACT-mediated nucleosome reorganization events. 10.1073/pnas.0712293105 JF - Proceedings of the National Academy of Sciences TI - The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module SP - 0712293105 KW - fact KW - spt16 AU - Stuwe, Tobias AU - Hothorn, Michael AU - Lejeune, Erwan AU - Rybin, Vladimir AU - Bortfeld, Miriam AU - Scheffzek, Klaus AU - Ladurner, Andreas PY - 2008/06/25/ UR - http://dx.doi.org/10.1073/pnas.0712293105 ER -