TY  - JOUR
AU  - Ukmar-Godec, Tina
AU  - Yu, Taekyung
AU  - Ibanez de Opakua, Alain
AU  - Pantoja, Christian F
AU  - Munari, Francesca
AU  - Zweckstetter, Markus
TI  - Conformational diversity of human HP1α.
JO  - Protein science
VL  - 33
IS  - 7
SN  - 0961-8368
CY  - Bethesda, Md.
PB  - Protein Society
M1  - DZNE-2024-00793
SP  - e5079
PY  - 2024
AB  - 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.
KW  - Chromobox Protein Homolog 5: chemistry
KW  - Chromosomal Proteins, Non-Histone: chemistry
KW  - Chromosomal Proteins, Non-Histone: genetics
KW  - Chromosomal Proteins, Non-Histone: metabolism
KW  - Humans
KW  - Models, Molecular
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Protein Domains
KW  - Protein Conformation
KW  - HP1α (Other)
KW  - AlphaFold (Other)
KW  - HP1α (Other)
KW  - NMR spectroscopy (Other)
KW  - chromatin (Other)
KW  - dynamics (Other)
KW  - residual dipolar couplings (Other)
KW  - Chromobox Protein Homolog 5 (NLM Chemicals)
KW  - Chromosomal Proteins, Non-Histone (NLM Chemicals)
KW  - CBX5 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38895997
C2  - pmc:PMC11187854
DO  - DOI:10.1002/pro.5079
UR  - https://pub.dzne.de/record/270413
ER  -