RRC ID 48800
Author Subramanian L, Medina-Pritchard B, Barton R, Spiller F, Kulasegaran-Shylini R, Radaviciute G, Allshire RC, Arockia Jeyaprakash A.
Title Centromere localization and function of Mis18 requires Yippee-like domain-mediated oligomerization.
Journal EMBO Rep
Abstract Mis18 is a key regulator responsible for the centromere localization of the CENP-A chaperone Scm3 in Schizosaccharomyces pombe and HJURP in humans, which establishes CENP-A chromatin that defines centromeres. The molecular and structural determinants of Mis18 centromere targeting remain elusive. Here, by combining structural, biochemical, and yeast genetic studies, we show that the oligomerization of S. pombe Mis18, mediated via its conserved N-terminal Yippee-like domain, is crucial for its centromere localization and function. The crystal structure of the N-terminal Yippee-like domain reveals a fold containing a cradle-shaped pocket that is implicated in protein/nucleic acid binding, which we show is required for Mis18 function. While the N-terminal Yippee-like domain forms a homodimer in vitro and in vivo, full-length Mis18, including the C-terminal α-helical domain, forms a homotetramer in vitro We also show that the Yippee-like domains of human Mis18α/Mis18β interact to form a heterodimer, implying a conserved structural theme for Mis18 regulation.
Volume 17(4)
Pages 496-507
Published 2016-4-1
DOI 10.15252/embr.201541520
PII embr.201541520
PMID 26921242
PMC PMC4818781
MeSH Carrier Proteins / chemistry* Carrier Proteins / genetics Carrier Proteins / metabolism* Centromere / genetics Centromere / physiology* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Crystallography, X-Ray DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Epigenesis, Genetic Molecular Chaperones / genetics Molecular Chaperones / metabolism Protein Domains Protein Multimerization Schizosaccharomyces / genetics Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / chemistry* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism*
IF 7.497
Times Cited 18
DNA material pDUAL-GFH41 (RDB06189)