3J07

Model of a 24mer alphaB-crystallin multimer

Summary for 3J07

• Entry DOI: 10.2210/pdb3j07/pdb
• Related: 2KLR
• EMDB information: 1776
• Descriptor: Alpha-crystallin B chain (1 entity in total)
• Functional Keywords: shsp, chaperone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 24
• Total formula weight: 484606.32

Authors

Jehle, S.,Vollmar, B.,Bardiaux, B.,Dove, K.K.,Rajagopal, P.,Gonen, T.,Oschkinat, H.,Klevit, R.E. (deposition date: 2011-04-27, release date: 2016-01-20, Last modification date: 2024-05-01)

Primary citation

Jehle, S.,Vollmar, B.S.,Bardiaux, B.,Dove, K.K.,Rajagopal, P.,Gonen, T.,Oschkinat, H.,Klevit, R.E.
N-terminal domain of {alpha}B-crystallin provides a conformational switch for multimerization and structural heterogeneity.
Proc.Natl.Acad.Sci.USA, 108:6409-6414, 2011

PubMed Abstract: The small heat shock protein (sHSP) αB-crystallin (αB) plays a key role in the cellular protection system against stress. For decades, high-resolution structural studies on heterogeneous sHSPs have been confounded by the polydisperse nature of αB oligomers. We present an atomic-level model of full-length αB as a symmetric 24-subunit multimer based on solid-state NMR, small-angle X-ray scattering (SAXS), and EM data. The model builds on our recently reported structure of the homodimeric α-crystallin domain (ACD) and C-terminal IXI motif in the context of the multimer. A hierarchy of interactions contributes to build multimers of varying sizes: Interactions between two ACDs define a dimer, three dimers connected by their C-terminal regions define a hexameric unit, and variable interactions involving the N-terminal region define higher-order multimers. Within a multimer, N-terminal regions exist in multiple environments, contributing to the heterogeneity observed by NMR. Analysis of SAXS data allows determination of a heterogeneity parameter for this type of system. A mechanism of multimerization into higher-order asymmetric oligomers via the addition of up to six dimeric units to a 24-mer is proposed. The proposed asymmetric multimers explain the homogeneous appearance of αB in negative-stain EM images and the known dynamic exchange of αB subunits. The model of αB provides a structural basis for understanding known disease-associated missense mutations and makes predictions concerning substrate binding and the reported fibrilogenesis of αB.

PubMed: 21464278
DOI: 10.1073/pnas.1014656108

Experimental method

ELECTRON MICROSCOPY (20 Å)
SOLID-STATE NMR (20 Å)
SOLUTION SCATTERING (20 Å)