Conformational diversity of human HP1α.
AlphaFold
HP1α
NMR spectroscopy
chromatin
dynamics
residual dipolar couplings
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
revised:
27
05
2024
received:
29
02
2024
accepted:
30
05
2024
medline:
19
6
2024
pubmed:
19
6
2024
entrez:
19
6
2024
Statut:
ppublish
Résumé
Heterochromatin protein 1 alpha (HP1α) is an evolutionarily conserved protein that binds chromatin and is important for gene silencing. The protein comprises 191 residues arranged into three disordered regions and two structured domains, the chromo and chromoshadow domain, which associates into a homodimer. While high-resolution structures of the isolated domains of HP1 proteins are known, the structural properties of full-length HP1α remain largely unknown. Using a combination of NMR spectroscopy and structure predictions by AlphaFold2 we provide evidence that the chromo and chromoshadow domain of HP1α engage in direct contacts resulting in a compact chromo/chromoshadow domain arrangement. We further show that HP1β and HP1γ have increased interdomain dynamics when compared to HP1α which may contribute to the distinct roles of different Hp1 isoforms in gene silencing and activation.
Substances chimiques
Chromobox Protein Homolog 5
107283-02-3
Chromosomal Proteins, Non-Histone
0
CBX5 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e5079Subventions
Organisme : European Research Council
ID : 787679
Pays : International
Informations de copyright
© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
Références
Bosch‐Presegue L, Raurell‐Vila H, Thackray JK, Gonzalez J, Casal C, Kane‐Goldsmith N, et al. Mammalian HP1 isoforms have specific roles in heterochromatin structure and organization. Cell Rep. 2017;21(8):2048–2057.
Bryan LC, Weilandt DR, Bachmann AL, Kilic S, Lechner CC, Odermatt PD, et al. Single‐molecule kinetic analysis of HP1‐chromatin binding reveals a dynamic network of histone modification and DNA interactions. Nucleic Acids Res. 2017;45(18):10504–10517.
Canzio D, Chang EY, Shankar S, Kuchenbecker KM, Simon MD, Madhani HD, et al. Chromodomain‐mediated oligomerization of HP1 suggests a nucleosome‐bridging mechanism for heterochromatin assembly. Mol Cell. 2011;41(1):67–81.
Eissenberg JC, Elgin SC. The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev. 2000;10(2):204–210.
Jones DO, Cowell IG, Singh PB. Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays. 2000;22(2):124–137.
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–589.
Jung YS, Zweckstetter M. Backbone assignment of proteins with known structure using residual dipolar couplings. J Biomol NMR. 2004;30(1):25–35.
Kilic S, Bachmann AL, Bryan LC, Fierz B. Multivalency governs HP1α association dynamics with the silent chromatin state. Nat Commun. 2015;6:7313.
Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017;547(7662):236–240.
Lipsitz RS, Tjandra N. Residual dipolar couplings in NMR structure analysis. Annu Rev Biophys Biomol Struct. 2004;33:387–413.
Mirdita M, Schutze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: making protein folding accessible to all. Nat Methods. 2022;19(6):679–682.
Mishima Y, Watanabe M, Kawakami T, Jayasinghe CD, Otani J, Kikugawa Y, et al. Hinge and chromoshadow of HP1α participate in recognition of K9 methylated histone H3 in nucleosomes. J Mol Biol. 2013;425(1):54–70.
Munari F, Rezaei‐Ghaleh N, Xiang S, Fischle W, Zweckstetter M. Structural plasticity in human heterochromatin protein 1β. PLoS One. 2013;8(4):e60887.
Munari F, Soeroes S, Zenn HM, Schomburg A, Kost N, Schroder S, et al. Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome. J Biol Chem. 2012;287(40):33756–33765.
Nishibuchi G, Machida S, Osakabe A, Murakoshi H, Hiragami‐Hamada K, Nakagawa R, et al. N‐terminal phosphorylation of HP1α increases its nucleosome‐binding specificity. Nucleic Acids Res. 2014;42(20):12498–12511.
Phan TM, Kim YC, Debelouchina GT, Mittal J. Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization. eLife. 2023;12:RP90820. https://doi.org/10.1101/2023.05.28.542535
Shen Y, Delaglio F, Cornilescu G, Bax A. TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR. 2009;44(4):213–223.
Smothers JF, Henikoff S. The hinge and chromo shadow domain impart distinct targeting of HP1‐like proteins. Mol Cell Biol. 2001;21(7):2555–2569.
Ukmar‐Godec T, Cima‐Omori MS, Yerkesh Z, Eswara K, Yu T, Ramesh R, et al. Multimodal interactions drive chromatin phase separation and compaction. Proc Natl Acad Sci USA. 2023;120(50):e2308858120.
Vakoc CR, Mandat SA, Olenchock BA, Blobel GA. Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol Cell. 2005;19(3):381–391.
Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, et al. AlphaFold protein structure database: massively expanding the structural coverage of protein‐sequence space with high‐accuracy models. Nucleic Acids Res. 2022;50(D1):D439–D444.
Zeng W, Ball AR Jr, Yokomori K. HP1: heterochromatin binding proteins working the genome. Epigenetics. 2010;5(4):287–292.
Zweckstetter M. NMR: prediction of molecular alignment from structure using the PALES software. Nat Protoc. 2008;3(4):679–690.
Zweckstetter M, Bax A. Evaluation of uncertainty in alignment tensors obtained from dipolar couplings. J Biomol NMR. 2002;23(2):127–137.