Linked Life Data

21464278

Source:http://linkedlifedata.com/resource/pubmed/id/21464278

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-4-20
pubmed:abstractText
The small heat shock protein (sHSP) ?B-crystallin (?B) 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 ?B oligomers. We present an atomic-level model of full-length ?B 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 ?-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 ?B in negative-stain EM images and the known dynamic exchange of ?B subunits. The model of ?B provides a structural basis for understanding known disease-associated missense mutations and makes predictions concerning substrate binding and the reported fibrilogenesis of ?B.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6409-14
pubmed:dateRevised
2011-10-19
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity.
pubmed:affiliation
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural