3C9D

Crystal structure of Vps75

Summary for 3C9D

• Entry DOI: 10.2210/pdb3c9d/pdb
• Related: 3C9B
• Descriptor: Vacuolar protein sorting-associated protein 75 (2 entities in total)
• Functional Keywords: chromatin, histone chaperone, nucleus, phosphoprotein, protein transport, transport, chaperone
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Nucleus : P53853
• Total number of polymer chains: 2
• Total formula weight: 60024.44

Authors

Berndsen, C.E.,Tsubota, T.,Lindner, S.E.,Lee, S.,Holton, J.M.,Kaufman, P.D.,Keck, J.L.,Denu, J.M. (deposition date: 2008-02-15, release date: 2008-08-12, Last modification date: 2024-02-21)

Primary citation

Berndsen, C.E.,Tsubota, T.,Lindner, S.E.,Lee, S.,Holton, J.M.,Kaufman, P.D.,Keck, J.L.,Denu, J.M.
Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75
Nat.Struct.Mol.Biol., 15:948-956, 2008

PubMed Abstract: Histone acetylation and nucleosome remodeling regulate DNA damage repair, replication and transcription. Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones. In vitro analysis of Rtt109 revealed that Vps75, a Nap1 family histone chaperone, could also stimulate Rtt109-dependent acetylation of H3K56. However, the molecular function of the Rtt109-Vps75 complex remains elusive. Here we have probed the molecular functions of Vps75 and the Rtt109-Vps75 complex through biochemical, structural and genetic means. We find that Vps75 stimulates the kcat of histone acetylation by approximately 100-fold relative to Rtt109 alone and enhances acetylation of K9 in the H3 histone tail. Consistent with the in vitro evidence, cells lacking Vps75 showed a substantial reduction (60%) in H3K9 acetylation during S phase. X-ray structural, biochemical and genetic analyses of Vps75 indicate a unique, structurally dynamic Nap1-like fold that suggests a potential mechanism of Vps75-dependent activation of Rttl09. Together, these data provide evidence for a multifunctional HAT-chaperone complex that acetylates histone H3 and deposits H3-H4 onto DNA, linking histone modification and nucleosome assembly.

PubMed: 19172748
DOI: 10.1038/nsmb.1459

Experimental method

X-RAY DIFFRACTION (2 Å)