Disorder in CENP-ACse4 tail-chaperone interaction facilitates binding with Ame1/Okp1 at the kinetochore

Shivangi Shukla; Anusri Bhattacharya; Parveen Sehrawat; Prakhar Agarwal; Rahul Shobhawat; Nikita Malik; Kalaiyarasi Duraisamy; Nithyakalyani Sri Rangan; Ramakrishna V Hosur; Ashutosh Kumar

doi:10.1016/j.str.2024.03.002

Disorder in CENP-A^Cse4 tail-chaperone interaction facilitates binding with Ame1/Okp1 at the kinetochore

Structure. 2024 Jun 6;32(6):690-705.e6. doi: 10.1016/j.str.2024.03.002. Epub 2024 Apr 1.

Affiliations

¹ Department of Bioscience and Bioengineering, Indian Institute of Technology, Mumbai, India.
² Department of Biophysics, University of Mumbai, Mumbai, India.
³ Centre for Advanced Protein Studies, Syngene International Limited, Bangalore, India.
⁴ Department of Bioscience and Bioengineering, Indian Institute of Technology, Mumbai, India. Electronic address: [email protected].

PMID: 38565139
DOI: 10.1016/j.str.2024.03.002

Abstract

The centromere is epigenetically marked by a histone H3 variant-CENP-A. The budding yeast CENP-A called Cse4, consists of an unusually long N-terminus that is known to be involved in kinetochore assembly. Its disordered chaperone, Scm3 is responsible for the centromeric deposition of Cse4 as well as in the maintenance of a segregation-competent kinetochore. In this study, we show that the Cse4 N-terminus is intrinsically disordered and interacts with Scm3 at multiple sites, and the complex does not gain any substantial structure. Additionally, the complex forms a synergistic association with an essential inner kinetochore component (Ctf19-Mcm21-Okp1-Ame1), and a model has been suggested to this effect. Thus, our study provides mechanistic insights into the Cse4 N-terminus-chaperone interaction and also illustrates how intrinsically disordered proteins mediate assembly of complex multiprotein networks, in general.

Keywords: Cse4 N-terminus; Scm3; centromere; chaperone; disorder; histone; kinetochore.

MeSH terms

Binding Sites
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / metabolism
Centromere Protein A / chemistry
Centromere Protein A / metabolism
Chromosomal Proteins, Non-Histone* / chemistry
Chromosomal Proteins, Non-Histone* / genetics
Chromosomal Proteins, Non-Histone* / metabolism
Cytoskeletal Proteins
DNA-Binding Proteins* / chemistry
DNA-Binding Proteins* / genetics
DNA-Binding Proteins* / metabolism
Intrinsically Disordered Proteins / chemistry
Intrinsically Disordered Proteins / metabolism
Kinetochores* / chemistry
Kinetochores* / metabolism
Microtubule-Associated Proteins
Models, Molecular
Molecular Chaperones / chemistry
Molecular Chaperones / metabolism
Protein Binding*
Saccharomyces cerevisiae Proteins* / chemistry
Saccharomyces cerevisiae Proteins* / genetics
Saccharomyces cerevisiae Proteins* / metabolism
Saccharomyces cerevisiae* / metabolism

Substances

Chromosomal Proteins, Non-Histone
Saccharomyces cerevisiae Proteins
CSE4 protein, S cerevisiae
DNA-Binding Proteins
Ame1 protein, S cerevisiae
Scm3 protein, S cerevisiae
Molecular Chaperones
Intrinsically Disordered Proteins
Centromere Protein A
CTF19 protein, S cerevisiae
Cell Cycle Proteins
Cytoskeletal Proteins
Microtubule-Associated Proteins