4JUT: Crystal Structure Of A Mutant Fragment Of Human Hspb6

Citation:
Abstract
ATP-independent small heat-shock proteins (sHSPs) are an essential component of the cellular chaperoning machinery. Under both normal and stress conditions, sHSPs bind partially unfolded proteins and prevent their irreversible aggregation. Canonical vertebrate sHSPs, such as the alpha-crystallins, form large polydisperse oligomers from which smaller, functionally active subspecies dissociate. Here we focus on human HSPB6 which, despite having considerable homology to the alpha-crystallins in both the N-terminal region and the signature alpha-crystallin domain (ACD), only forms dimers in solution that represent the basic chaperoning subspecies. We addressed the three-dimensional structure and functional properties of HSPB6 in a hybrid study employing X-ray crystallography, solution small-angle X-ray scattering (SAXS), mutagenesis, size-exclusion chromatography and chaperoning assays. The crystal structure of a proteolytically stable fragment reveals typical ACD dimers which further form tetrameric assemblies as a result of extensive inter-dimer patching of the beta4/beta8 grooves. The patching is surprisingly mediated by tripeptide motifs, found in the N-terminal domain directly adjacent to the ACD, that are resembling but distinct from the canonical IxI sequence commonly binding this groove. By combining the crystal structure with SAXS data for the full-length protein, we derive a molecular model of the latter. In solution, HSPB6 shows a strong attractive self-interaction, a property that correlates with its chaperoning activity. Both properties are dictated by the unstructured yet compact N-terminal domain, specifically a region highly conserved across vertebrate sHSPs.
PDB ID: 4JUTDownload
MMDB ID: 117241
PDB Deposition Date: 2013/3/25
Updated in MMDB: 2014/02
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4JUT: tetrameric; determined by author and by software (PISA)
Molecular Components in 4JUT
Label Count Molecule
Proteins (4 molecules)
4
Heat Shock Protein Beta-6(Gene symbol: HSPB6)
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

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