Journal Article

DZNE-2024-00793

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Conformational diversity of human HP1α.

Ukmar-Godec, T. (First author)DZNE* ; Yu, T.DZNE* ; Ibanez de Opakua, A.DZNE* ; Pantoja, C. F.DZNE* ; Munari, F. ; Zweckstetter, M. (Last author)DZNE*

2024
Protein Society Bethesda, Md.

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Please use a persistent id in citations: doi:10.1002/pro.5079

Abstract: 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.

Keyword(s): Chromobox Protein Homolog 5: chemistry (MeSH) ; Chromosomal Proteins, Non-Histone: chemistry (MeSH) ; Chromosomal Proteins, Non-Histone: genetics (MeSH) ; Chromosomal Proteins, Non-Histone: metabolism (MeSH) ; Humans (MeSH) ; Models, Molecular (MeSH) ; Nuclear Magnetic Resonance, Biomolecular (MeSH) ; Protein Domains (MeSH) ; Protein Conformation (MeSH) ; HP1α ; AlphaFold ; HP1α ; NMR spectroscopy ; chromatin ; dynamics ; residual dipolar couplings ; Chromobox Protein Homolog 5 ; Chromosomal Proteins, Non-Histone ; CBX5 protein, human

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Contributing Institute(s):

1. Translational Structural Biology (AG Zweckstetter)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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