Linked Life Data

21857680

Source:http://linkedlifedata.com/resource/pubmed/id/21857680

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7362
pubmed:dateCreated
2011-9-2
pubmed:databankReference
pubmed:abstractText
Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers). However, a rigorous understanding of the relation between a protein's structure, dynamics and function remains elusive. This is because many of the conformers on its energy landscape are only transiently formed and marginally populated (less than a few per cent of the total number of molecules), so that they cannot be individually characterized by most biophysical tools. Here we study a lysozyme mutant from phage T4 that binds hydrophobic molecules and populates an excited state transiently (about 1?ms) to about 3% at 25?°C (ref. 5). We show that such binding occurs only via the ground state, and present the atomic-level model of the 'invisible', excited state obtained using a combined strategy of relaxation-dispersion NMR (ref. 6) and CS-Rosetta model building that rationalizes this observation. The model was tested using structure-based design calculations identifying point mutants predicted to stabilize the excited state relative to the ground state. In this way a pair of mutations were introduced, inverting the relative populations of the ground and excited states and altering function. Our results suggest a mechanism for the evolution of a protein's function by changing the delicate balance between the states on its energy landscape. More generally, they show that our approach can generate and validate models of excited protein states.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
477
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-4
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Solution structure of a minor and transiently formed state of a T4 lysozyme mutant.
pubmed:affiliation
Department of Molecular Genetics, The University of Toronto, Toronto, Ontario M5S 1A8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't