Abstract:
:Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cAMP to the dimeric catabolite activator protein (CAP) at discrete conformational states. Binding of the first cAMP to one subunit of a CAP dimer has no effect on the conformation of the other subunit. The dynamics of the system, however, are modulated in a distinct way by the sequential ligand binding process, with the first cAMP partially enhancing and the second cAMP completely quenching protein motions. As a result, the second cAMP binding incurs a pronounced conformational entropic penalty that is entirely responsible for the observed cooperativity. The results provide strong support for the existence of purely dynamics-driven allostery.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Popovych N,Sun S,Ebright RH,Kalodimos CGdoi
10.1038/nsmb1132subject
Has Abstractpub_date
2006-09-01 00:00:00pages
831-8issue
9eissn
1545-9993issn
1545-9985pii
nsmb1132journal_volume
13pub_type
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