A backbone-reversed form of an all-beta alpha-crystallin domain from a small heat-shock protein (retro-HSP12.6) folds and assembles into structured multimers.
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
A backbone-reversed form of an all-beta alpha-crystallin domain from a small heat-shock protein (retro-HSP12.6) folds and assembles into structured multimers.
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Creator |
Shukla, Anshuman
Raje, Manoj Guptasarma, Purnananda |
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Subject |
QD Chemistry
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Description |
The structural consequences of polypeptide backbone reversal ("retro" modification) remain largely unexplored, in particular, for the retro forms of globular all-beta-sheet proteins. To examine whether the backbone-reversed form of a model all-beta-sheet protein can fold and adopt secondary and tertiary structure, we created and examined the recombinant retro form of a 110-residue-long polypeptide, an alpha-crystallin-like small heat-shock protein, HSP12.6, from C. elegans. Following intracellular overexpression in fusion with a histidine affinity tag in Escherichia coli, purification under denaturing conditions, and removal of denaturant through dialysis, retro-HSP12.6 was found to fold to a soluble state. The folded protein was examined using fluorescence and CD spectroscopy, gel filtration chromatography, non-denaturing electrophoresis, differential scanning calorimetry, and electron microscopy and confirmed to have adopted secondary structure and assembled into a multimer. Interestingly, like its parent polypeptide, retro-HSP12.6 did not aggregate upon heating; rather, heating led to a dramatic increase in structural content and the adoption of what would appear to be a very well folded state at high temperatures. However, this was essentially reversed upon cooling with some hysteresis being observed resulting in greater structural content in the heated-cooled protein than in the unheated protein. The heated-cooled samples displayed CD spectra indicative of structural content comparable to that of any naturally occurring globular protein. Attempts are being made to refine crystallization conditions for the folded protein.
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Publisher |
ASBMB
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Date |
2003-07-18
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://crdd.osdd.net/open/247/1/guptasarma2003.1.pdf
Shukla, Anshuman and Raje, Manoj and Guptasarma, Purnananda (2003) A backbone-reversed form of an all-beta alpha-crystallin domain from a small heat-shock protein (retro-HSP12.6) folds and assembles into structured multimers. The Journal of biological chemistry, 278 (29). pp. 26505-10. ISSN 0021-9258 |
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Relation |
http://www.jbc.org/content/278/29/26505.full.pdf+html
http://crdd.osdd.net/open/247/ |
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