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Title: Recognition of the centromere-specific histone Cse4 by the chaperone Scm3

Abstract

A specialized nucleosome is a component of all eukaryotic kinetochores. The core of this nucleosome contains a centromere-specific histone, CENP-A (the Cse4 gene product in budding yeast), instead of the usual H3. Assembly of a centromeric nucleosome depends on a specific chaperone, called Scm3 in yeast and HJURP in higher eukaryotes. We describe here the structure of a complex formed by an N-terminal fragment of Scm3 with the histone-fold domains of Cse4, and H4, all prepared as recombinant proteins derived from the budding yeast Kluyveromyces lactis. The contacts of Scm3 with Cse4 explain its selectivity for the centromere-specific histone; key residues at the interface are conserved in HJURP, indicating a common mechanism for centromeric-histone deposition. We also report the structure of a (Cse4 : H4)2 heterotetramer; comparison with the structure of the Scm3:Cse4:H4 complex shows that tetramer formation and DNA-binding require displacement of Scm3 from the nucleosome core. The two structures together suggest that specific contacts between the chaperone and Cse4, rather than an altered overall structure of the nucleosome core, determine the selective presence of Cse4 at centromeres.

Authors:
;  [1]
  1. (Harvard-Med)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
UNIVERSITYHHMI
OSTI Identifier:
1023666
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (23) ; 06, 2011; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; CENTROMERES; DEPOSITION; GENES; HISTONES; INTERFACES; NUCLEOSOMES; PROTEINS; RESIDUES; YEASTS

Citation Formats

Cho, Uhn-Soo, and Harrison, Stephen C. Recognition of the centromere-specific histone Cse4 by the chaperone Scm3. United States: N. p., 2011. Web. doi:10.1073/pnas.1106389108.
Cho, Uhn-Soo, & Harrison, Stephen C. Recognition of the centromere-specific histone Cse4 by the chaperone Scm3. United States. doi:10.1073/pnas.1106389108.
Cho, Uhn-Soo, and Harrison, Stephen C. Tue . "Recognition of the centromere-specific histone Cse4 by the chaperone Scm3". United States. doi:10.1073/pnas.1106389108.
@article{osti_1023666,
title = {Recognition of the centromere-specific histone Cse4 by the chaperone Scm3},
author = {Cho, Uhn-Soo and Harrison, Stephen C.},
abstractNote = {A specialized nucleosome is a component of all eukaryotic kinetochores. The core of this nucleosome contains a centromere-specific histone, CENP-A (the Cse4 gene product in budding yeast), instead of the usual H3. Assembly of a centromeric nucleosome depends on a specific chaperone, called Scm3 in yeast and HJURP in higher eukaryotes. We describe here the structure of a complex formed by an N-terminal fragment of Scm3 with the histone-fold domains of Cse4, and H4, all prepared as recombinant proteins derived from the budding yeast Kluyveromyces lactis. The contacts of Scm3 with Cse4 explain its selectivity for the centromere-specific histone; key residues at the interface are conserved in HJURP, indicating a common mechanism for centromeric-histone deposition. We also report the structure of a (Cse4 : H4)2 heterotetramer; comparison with the structure of the Scm3:Cse4:H4 complex shows that tetramer formation and DNA-binding require displacement of Scm3 from the nucleosome core. The two structures together suggest that specific contacts between the chaperone and Cse4, rather than an altered overall structure of the nucleosome core, determine the selective presence of Cse4 at centromeres.},
doi = {10.1073/pnas.1106389108},
journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (23) ; 06, 2011,
volume = 108,
place = {United States},
year = {2011},
month = {9}
}