Linked Life Data

10543974

Source:http://linkedlifedata.com/resource/pubmed/id/10543974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-12-30
pubmed:abstractText
Calmodulin undergoes Ca2+-induced structural rearrangements that are intimately coupled to the regulation of numerous cellular processes. The C-terminal domain of calmodulin has previously been observed to exhibit conformational exchange in the absence of Ca2+. Here, we characterize further the conformational dynamics in the presence of low concentrations of Ca2+ using 15N spin relaxation experiments. The analysis included 1H-15N dipolar/15N chemical shift anisotropy interference cross-correlation relaxation rates to improve the description of the exchange processes, as well as the picosecond to nanosecond dynamics. Conformational transitions on microsecond to millisecond time scales were revealed by exchange contributions to the transverse auto-relaxation rates. In order to separate the effects of Ca2+ exchange from intramolecular conformational exchange processes in the apo state, transverse auto-relaxation rates were measured at different concentrations of free Ca2+. The results reveal a Ca2+-dependent contribution due mainly to exchange between the apo and (Ca2+)1 states with an apparent Ca2+ off-rate of approximately 5115 s(-1), as well as Ca2+-independent contributions due to conformational exchange within the apo state. 15N chemical shift differences estimated from the exchange data suggest that the first Ca2+ binds preferentially to loop IV. Thus, characterization of chemical exchange as a function of Ca2+ concentration has enabled the extraction of unique information on the rapidly exchanging and weakly populated (<10 %) (Ca2+)1 state that is otherwise inaccessible to direct study due to strongly cooperative Ca2+ binding. The conformational exchange within the apo state appears to involve transitions between a predominantly populated closed conformation and a smaller population of more open conformations. The picosecond to nanosecond dynamics of the apo state are typical of a well-folded protein, with reduced amplitudes of motions in the helical segments, but with significant flexibility in the Ca2+-binding loops. Comparisons with order parameters for skeletal troponin C and calbindin D9k reveal key structural and dynamical differences that correlate with the different Ca2+-binding properties of these proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
883-99
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Structural dynamics in the C-terminal domain of calmodulin at low calcium levels.
pubmed:affiliation
Physical Chemistry 2, Lund University, Lund, S-221 00, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't