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Structural Insights Into the Hir Histone Chaperone Complex / Hee Jong Kim.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Kim, Hee Jong, author.
- Language:
- English
- Subjects (All):
- Biochemistry.
- Biophysics.
- Molecular biology.
- Genetics.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Local Subjects:
- Biochemistry.
- Biophysics.
- Molecular biology.
- Genetics.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Physical Description:
- 1 online resource (92 pages)
- Distribution:
- Ann Arbor : ProQuest Dissertations & Theses, 2023
- Contained In:
- Dissertations Abstracts International 85-08B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Language Note:
- English
- Summary:
- The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 tetramers into nucleosomes for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition has remained unknown since its initial identification nearly three decades ago. Here we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9-6.8 A resolution, together with crosslinking mass spectrometry, yeast genetic, and biochemical analyses. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4 with a central cavity in which two copies of Hpc2 from each sub-complex within the dimer are in suitable position to accommodate a histone (H3-H4)2 tetramer. The core of the complex contains Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3, while C-terminal segments of Hir3 harbor nucleic acid binding properties implicated for double-stranded DNA engagement within the cavity for histone deposition. Despite the near two-fold symmetric scaffold, the structure reveals only one bound Asf1/H3/H4 complex in the cavity, with another presumed Asf1/H3/H4 complex poised outside of the cavity, suggesting a synergetic mechanism for HIRA/Hir-mediated histone deposition in which the Hpc2-assisted energetically unfavorable (H3/H4)2 tetramer can be immediately wrapped by DNA positioned by Hir3.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-08, Section: B.
- Advisors: Murakami, Kenji; Sharp, Kim A.; Committee members: Black, Ben E.; Chang, Yi-Wei; Petersson, E. James; Kalisman, Nir.
- Department: Biochemistry and Molecular Biophysics.
- Ph.D. University of Pennsylvania 2023.
- Local Notes:
- School code: 0175
- ISBN:
- 9798381510935
- Access Restriction:
- Restricted for use by site license.
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