6MUP

CENP-A nucleosome bound by two copies of CENP-C(CD) and two copies CENP-N(NT)

6MUP の概要

• エントリーDOI: 10.2210/pdb6mup/pdb
• 関連するPDBエントリー: 6MUO
• EMDBエントリー: 9250 9251 9252
• 分子名称: Histone H3-like centromeric protein A, Histone H4, Histone H2A type 1-C, ... (8 entities in total)
• 機能のキーワード: centromere, cenp-a, kinetochore, nucleosome, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 234530.89

構造登録者

Allu, P.K.,Black, B.E. (登録日: 2018-10-23, 公開日: 2019-07-24, 最終更新日: 2024-03-13)

主引用文献

Allu, P.K.,Dawicki-McKenna, J.M.,Van Eeuwen, T.,Slavin, M.,Braitbard, M.,Xu, C.,Kalisman, N.,Murakami, K.,Black, B.E.
Structure of the Human Core Centromeric Nucleosome Complex.
Curr.Biol., 29:2625-2639.e5, 2019

PubMed Abstract: Centromeric nucleosomes are at the interface of the chromosome and the kinetochore that connects to spindle microtubules in mitosis. The core centromeric nucleosome complex (CCNC) harbors the histone H3 variant, CENP-A, and its binding proteins, CENP-C (through its central domain; CD) and CENP-N (through its N-terminal domain; NT). CENP-C can engage nucleosomes through two domains: the CD and the CENP-C motif (CM). CENP-C is part of the CCNC by virtue of its high specificity for CENP-A nucleosomes and ability to stabilize CENP-A at the centromere. CENP-C is thought to engage a neighboring nucleosome, either one containing conventional H3 or CENP-A, and a crystal structure of a nucleosome complex containing two copies of CENP-C was reported. Recent structures containing a single copy of CENP-N bound to the CENP-A nucleosome in the absence of CENP-C were reported. Here, we find that one copy of CENP-N is lost for every two copies of CENP-C on centromeric chromatin just prior to kinetochore formation. We present the structures of symmetric and asymmetric forms of the CCNC that vary in CENP-N stoichiometry. Our structures explain how the central domain of CENP-C achieves its high specificity for CENP-A nucleosomes and how CENP-C and CENP-N sandwich the histone H4 tail. The natural centromeric DNA path in our structures corresponds to symmetric surfaces for CCNC assembly, deviating from what is observed in prior structures using artificial sequences. At mitosis, we propose that CCNC asymmetry accommodates its asymmetric connections at the chromosome/kinetochore interface. VIDEO ABSTRACT.

PubMed: 31353180
DOI: 10.1016/j.cub.2019.06.062

実験手法

ELECTRON MICROSCOPY (3.5 Å)