title: Structural plasticity in human heterochromatin protein 1β.
abstract: As essential components of the molecular machine assembling heterochromatin in eukaryotes, HP1 (Heterochromatin Protein 1) proteins are key regulators of genome function. While several high-resolution structures of the two globular regions of HP1, chromo and chromoshadow domains, in their free form or in complex with recognition-motif peptides are available, less is known about the conformational behavior of the full-length protein. Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners. In addition, the binding pockets within the chromo and chromoshadow domains experience internal dynamics that can be useful for the versatile recognition of different binding partners. In particular, we provide evidence for the presence of a distinct structural propensity in free hHP1β that prepares a binding-competent interface for the formation of the intermolecular β-sheet with methylated histone H3. The structural plasticity of hHP1β supports its ability to bind and connect a wide variety of binding partners in epigenetic processes.
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Munari
authors.forename: Nasrollah
authors.initials: N
authors.lastname: Rezaei-Ghaleh
authors.forename: Shengqi
authors.initials: S
authors.lastname: Xiang
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischle
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D001665:Binding Sites; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000737:chemistry* / Q000235:genetics; D006657:Histones / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D053838:Scattering, Small Angle; D012996:Solutions
chemical_list: C000715593:CBX1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D011994:Recombinant Proteins; D012996:Solutions; D000090266:Chromobox Protein Homolog 5