Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-28
pubmed:abstractText
How tightly packed is the hydrophobic core of a folding transition state structure? We have addressed this question by characterizing the effects on folding kinetics of > 40 substitutions of both large and small amino acids in the hydrophobic core of the Fyn SH3 domain. Our results show that residues at three positions, which we designate as the 'core folding nucleus', are tightly packed in the transition state, and substitutions at these positions cause the largest changes in the folding rate. The other six positions examined appear to be loosely packed; thus, substitutions at these positions with larger hydrophobic residues generally accelerate folding, presumably by increasing the rate of nonspecific hydrophobic collapse. Surprisingly, the folding rate can be greatly accelerated by residues that also significantly destabilize the native state structure. Furthermore, mutants with identical thermodynamic stability can differ by up to 55-fold in their folding rates. These results highlight the importance of hydrophobic core composition, as opposed to only topology, in determining the folding rate of a protein. They also provide a new explanation for the 'abnormal' phi-values observed in many protein folding kinetics studies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1072-8368
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
126-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Hydrophobic core packing in the SH3 domain folding transition state.
pubmed:affiliation
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't