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The Transition Stat...
The Transition State of Coupled Folding and Binding for a Flexible beta-Finger
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- Karlsson, O. Andreas (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Chi, Celestine N., 1978- (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,ETH, Lab Phys Chem, Zurich, Switzerland,Chi Celestine
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- Engström, Åke (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Jemth, Per (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 417:3, s. 253-261
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Flexible and fully disordered protein regions that fold upon binding mediate numerous protein protein interactions. However, little is known about their mechanism of interaction. One such coupled folding and binding occurs when a flexible region of neuronal nitric oxide synthase adopts a beta-finger structure upon binding to its protein ligand, a PDZ [PSD-95 (postsynaptic density protein-95)/Discs large/ZO-1] domain from PSD-95. We have analyzed this binding reaction by protein engineering combined with kinetic experiments. Mutational destabilization of the beta-finger changed mainly the dissociation rate constant of the proteins and, to a lesser extent, the association rate constant. Thus, mutation affected late events in the coupled folding and binding reaction. Our results therefore suggest that the native binding interactions of the beta-finger are not present in the rate-limiting transition state for binding but form on the downhill side in a cooperative manner. However, by mutation, we could destabilize the beta-finger further and change the rate-limiting step such that an initial conformational change becomes rate limiting. This switch in rate-limiting step shows that multistep binding mechanisms are likely to be found among flexible and intrinsically disordered regions of proteins.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- intrinsically disordered proteins
- PDZ domain
- binding kinetics
- phi binding
- flexible proteins
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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