7C5D

Crystal structure of TRF2 TRFH domain in complex with a MCPH1 peptide

7C5D の概要

• エントリーDOI: 10.2210/pdb7c5d/pdb
• 分子名称: Telomeric repeat-binding factor 2, Microcephalin, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: telomere, shelterin complex, trf2, mcph1, dna repair, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 52492.76

構造登録者

Xiong, X.,Chen, Y. (登録日: 2020-05-19, 公開日: 2020-10-21, 最終更新日: 2023-11-29)

主引用文献

Cicconi, A.,Rai, R.,Xiong, X.,Broton, C.,Al-Hiyasat, A.,Hu, C.,Dong, S.,Sun, W.,Garbarino, J.,Bindra, R.S.,Schildkraut, C.,Chen, Y.,Chang, S.
Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly.
Nat Commun, 11:5861-5861, 2020

PubMed Abstract: Telomeres protect chromosome ends from inappropriately activating the DNA damage and repair responses. Primary microcephaly is a key clinical feature of several human telomere disorder syndromes, but how microcephaly is linked to dysfunctional telomeres is not known. Here, we show that the microcephalin 1/BRCT-repeats inhibitor of hTERT (MCPH1/BRIT1) protein, mutated in primary microcephaly, specifically interacts with the TRFH domain of the telomere binding protein TRF2. The crystal structure of the MCPH1-TRF2 complex reveals that this interaction is mediated by the MCPH1 YRLSP motif. TRF2-dependent recruitment of MCPH1 promotes localization of DNA damage factors and homology directed repair of dysfunctional telomeres lacking POT1-TPP1. Additionally, MCPH1 is involved in the replication stress response, promoting telomere replication fork progression and restart of stalled telomere replication forks. Our work uncovers a previously unrecognized role for MCPH1 in promoting telomere replication, providing evidence that telomere replication defects may contribute to the onset of microcephaly.

PubMed: 33203878
DOI: 10.1038/s41467-020-19674-0

実験手法

X-RAY DIFFRACTION (2.151 Å)