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How Do Small Heat Shock Proteins Function?
Author(s) -
Rajagopal Ponni,
Jehle Stefan,
Caputo Christine,
Cho SeungHee,
Oschkinat Hartmut,
Klevit Rachel
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.672.2
Subject(s) - desmin , dimer , chemistry , biophysics , mutant , chaperone (clinical) , oligomer , crystallin , heat shock protein , monomer , dissociation (chemistry) , fiber diffraction , cysteine , biochemistry , microbiology and biotechnology , biology , enzyme , x ray crystallography , medicine , vimentin , immunohistochemistry , physics , organic chemistry , pathology , gene , diffraction , optics , immunology , polymer
We are investigating the structure of human αB‐Crystallin (αB), an archetypal member of the small Heat Shock Protein (sHSP) family using an hybrid solid‐solution state NMR approach and probing functional questions with the α‐crystallin domain that's common to all sHSPs. The polydisperse, ~580 kDa αB is assembled from 20 kDa subunits and has an 89‐residue α‐crystallin domain. We have isolated the α‐crystallin domain (αB10.1) for solution NMR studies and we are using solid‐state NMR to investigate the structure of αB. The dimeric α‐crystallin domain has an unique structure that's maintained in both the isolated and oligomeric forms. The unusual architecture may provide key answers to the functional mechanisms of αB. αB binds cardiac muscle proteins such as desmin and titin more tightly at acidic pH values presumably to maintain filament integrity of these proteins during cardiac ischemia which is accompanied by acidosis. A mutant, R120G‐αB, is associated with desmin‐related cardio‐myopathy. αB10.1 undergoes a sharp pH‐dependent dimer‐monomer transition in contrast to the mutant R120G‐αB10.1. pH‐dependent dissociation of the α‐crystallin domain can lead to disruption of the oligomer assembly, an event that's postulated to be essential for sHSP function. The absence of this dissociation in the mutant abrogates its protective role, thereby explaining its disease association. Funding from NEI, 1R01EY017370