help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vigil, D.
Right arrow Articles by García, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vigil, D.
Right arrow Articles by García, A. E.

Biophys J, May 2001, p. 2082-2092, Vol. 80, No. 5

Functional Dynamics of the Hydrophobic Cleft in the N-Domain of Calmodulin

Dominico Vigil,* Stephen C. Gallagher,dagger Jill Trewhella,dagger and Angel E. García*

 *Theoretical Biology and Biophysics Group, T10 MS K710, and  dagger Biosciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 USA

Molecular dynamics studies of the N-domain (amino acids 1-77; CaM1-77) of Ca2+-loaded calmodulin (CaM) show that a solvent exposed hydrophobic cleft in the crystal structure of CaM exhibits transitions from an exposed (open) to a buried (closed) state over a time scale of nanoseconds. As a consequence of burying the hydrophobic cleft, the Rg of the protein is reduced by 1.5 Å. Based on this prediction, x-ray scattering experiments were conducted on this domain over a range of concentrations. Models built from the scattering data show that the Rg and general shape is consistent with the simulation studies of CaM1-77. Based on these observations we postulate a model in which the conformation of CaM fluctuates between two different states that expose and bury this hydrophobic cleft. In aqueous solution the closed state dominates the population, while in the presence of peptides, the open state dominates. This inherent flexibility of CaM may be the key to its versatility in recognizing structurally distinct peptide sequences. This model conflicts with the currently accepted hypothesis based on observations in the crystal structure, where upon Ca2+ binding the hydrophobic cleft is exposed to solvent. We postulate that crystal packing forces stabilize the protein conformation toward the open configuration.

Biophys J, May 2001, p. 2082-2092, Vol. 80, No. 5
© 2001 by the Biophysical Society   0006-3495/01/05/2082/11  $2.00


This article has been cited by other articles:


Home page
 Biophys. JHome page
A. Ganoth, R. Friedman, E. Nachliel, and M. Gutman
A Molecular Dynamics Study and Free Energy Analysis of Complexes between the Mlc1p Protein and Two IQ Motif Peptides
Biophys. J., October 1, 2006; 91(7): 2436 - 2450.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
C. Kobayashi and S. Takada
Protein Grabs a Ligand by Extending Anchor Residues: Molecular Simulation for Ca2+ Binding to Calmodulin Loop
Biophys. J., May 1, 2006; 90(9): 3043 - 3051.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
C. M. Shepherd and H. J. Vogel
A Molecular Dynamics Study of Ca2+-Calmodulin: Evidence of Interdomain Coupling and Structural Collapse on the Nanosecond Timescale
Biophys. J., August 1, 2004; 87(2): 780 - 791.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
V. A. Likic, E. E. Strehler, and P. R. Gooley
Dynamics of Ca2+-saturated calmodulin D129N mutant studied by multiple molecular dynamics simulations
Protein Sci., October 1, 2003; 12(10): 2215 - 2229.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Biophysical Society.