title: Human βB2-Crystallin Forms a Face-en-Face Dimer in Solution: An Integrated NMR and SAXS Study.
abstract: βγ-Crystallins are long-lived eye lens proteins that are crucial for lens transparency and refractive power. Each βγ-crystallin comprises two homologous domains, which are connected by a short linker. γ-Crystallins are monomeric, while β-crystallins crystallize as dimers and multimers. In the crystal, human βB2-crystallin is a domain-swapped dimer while the N-terminally truncated βB1-crystallin forms a face-en-face dimer. Combining and integrating data from multi-angle light scattering, nuclear magnetic resonance, and small-angle X-ray scattering of full-length and terminally truncated human βB2-crystallin in solution, we show that both these βB2-crystallin proteins are dimeric, possess C2 symmetry, and are more compact than domain-swapped dimers. Importantly, no inter-molecular paramagnetic relaxation enhancement effects compatible with domain swapping were detected. Our collective experimental results unambiguously demonstrate that, in solution, human βB2-crystallin is not domain swapped and exhibits a face-en-face dimer structure similar to the crystal structure of truncated βB1-crystallin.
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Whitley
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: amg100@pitt.edu.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D053838:Scattering, Small Angle; D017384:Sequence Deletion; D014961:X-Ray Diffraction; D038206:beta-Crystallin B Chain / Q000737:chemistry* / Q000235:genetics*
chemical_list: D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2
keywords: MALS; NMR; PRE; SAXS; cataract; domain swapping; eye lens; integrated structural biology; spin label; βB2-crystallin