Calmodulin’s flexibility allows for promiscuity in its interactions with target proteins and peptides

@article{Yamniuk2004CalmodulinsFA,
  title={Calmodulin’s flexibility allows for promiscuity in its interactions with target proteins and peptides},
  author={Aaron P. Yamniuk and Hans J. Vogel},
  journal={Molecular Biotechnology},
  year={2004},
  volume={27},
  pages={33-57}
}
The small bilobal calcium regulatory protein calmodulin (CaM) activates numerous target enzymes in response to transient changes in intracellular calcium concentrations. Binding of calcium to the two helix-loop-helix calcium-binding motifs in each of the globular domains induces conformational changes that expose a methionine-rich hydrophobic patch on the surface of each domain of the protein, which it uses to bind to peptide sequences in its target enzymes. Although these CaM-binding domains… Expand
Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding
TLDR
Martini coarse-grained molecular dynamics simulations are utilized to probe CaM/target assembly for a model system: CaM binding to the calcineurin (CaN) regulatory domain and suggest variations in the CaM linker’s propensity for alpha helical secondary structure can modulate the kinetics of target binding. Expand
A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization
TLDR
Calmodulin sequestration of the KRas4b farnesyl moiety disrupts KRAS4b membrane association and downstream signaling and is proposed to comprise a non-canonical CaM-binding motif. Expand
Structural and thermodynamic characterization of the recognition of the S100‐binding peptides TRTK12 and p53 by calmodulin
TLDR
This study demonstrates the plasticity of CaM in target binding and may suggest a possible overlap in target specificity between CaM and the S100 proteins. Expand
Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding
TLDR
Variations in the CaM linker’s propensity for alpha-helical secondary structure can modulate the kinetics of target binding, which is important, as the linker region houses several CaM variants sites for post-translational modifications, that may alter the protein’'s normal regulatory functions. Expand
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1
TLDR
The first high-resolution NMR structure of α-actinin-1's functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form is determined, revealing a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Expand
Conformational frustration in calmodulin–target recognition
TLDR
The molecular basis of target recognition of CaM with peptides representing the CaM‐binding domains from two Ca2+‐CaM‐dependent kinases, CaMKI and CaMKII, is explored by employing experimentally constrained molecular simulations. Expand
Calmodulin has the Potential to Function as a Ca2+-Dependent Adaptor Protein
TLDR
It is hypothesized that CaM may be capable of functioning as a Ca2+-dependent adaptor or recruiter protein, although the dimerization mechanism is distinct from the previously described simultaneous binding of other target peptides to CaM. Expand
Single-molecule force spectroscopy distinguishes target binding modes of calmodulin
  • J. Junker, M. Rief
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences
  • 2009
TLDR
Investigation of fluctuations of the complex formation of CaM and its target peptide sequences using single-molecule force spectroscopy by AFM reveals an association mode for CaMKK in which the peptide binds strongly to only partially Ca2+-saturated CaM, which might allow for a fine-tuning of the intracellular response to changes inCa2+ concentration. Expand
Peptide binding by a fragment of calmodulin composed of EF-hands 2 and 3.
TLDR
It is demonstrated that Ca2+-ligated CaM2/3 can also bind to a peptide representing the CaM-recognition sequence of skeletal muscle myosin light chain kinase (M13) with an equimolar stoichiometry and a dissociation constant of 0.40 +/- 0.05 microM. Expand
PEP-19 modulates calcium binding to calmodulin by electrostatic steering
TLDR
The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca2+ binding to the C-domain of CaM by ‘catching' and electrostatically steering Ca 2+ to site III. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 144 REFERENCES
Protein engineering and NMR studies of calmodulin
The calcium regulatory protein calmodulin (CaM) plays a role as an on-off switch in the activation of many enzymes and proteins. CaM has a dumbbell shaped structure with two folded domains, which areExpand
Variable conformation and dynamics of calmodulin complexed with peptides derived from the autoinhibitory domains of target proteins.
TLDR
Calcium-saturated calmodulin can bind and activate many target proteins through the direct association with the respective autoinhibitory domains, but there are significant differences in the observed lifetime, solvent accessibility, correlation time associated with the segmented rotational motion of PM-CaM, which indicates that CaM adopts a different tertiary structure that is dependent on the structural features of the bound target peptide. Expand
The calmodulin-binding domain of caldesmon binds to calmodulin in an alpha-helical conformation.
TLDR
Two dimensional NMR studies performed in aqueous TFE mixture showed that the CaD peptide has the capacity to adopt an amphiphilic alpha-helical conformation and chemical shifts suggest that both domains and the central helix of CaM are involved in the binding of the peptide. Expand
Solution structure of a calmodulin-target peptide complex by multidimensional NMR.
The three-dimensional solution structure of the complex between calcium-bound calmodulin (Ca(2+)-CaM) and a 26-residue synthetic peptide comprising the CaM binding domain (residues 577 to 602) ofExpand
Calcium-Calmodulin-induced Dimerization of the Carboxyl-terminal Domain from Petunia Glutamate Decarboxylase
  • T. Yuan, H. Vogel
  • Chemistry, Medicine
  • The Journal of Biological Chemistry
  • 1998
TLDR
The results predict that binding of calcium-CaM to PGD will give rise to dimerization of the protein, which may be necessary for activation. Expand
Sequence motifs for calmodulin recognition
  • A. Rhoads, F. Friedberg
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1997
TLDR
Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins and a modified version of the IQ motif as a consensus for Ca2+‐independent binding and two related motifs, termed 18‐14 and 1‐5‐10 based on the position of conserved hydrophobic residues, are proposed. Expand
Structure of the Complex of Calmodulin with the Target Sequence of Calmodulin-Dependent Protein Kinase I: Studies of the Kinase Activation Mechanism‡
Calcium-saturated calmodulin (CaM) directly activates CaM-dependent protein kinase I (CaMKI) by binding to a region in the C-terminal regulatory sequence of the enzyme to relieve autoinhibition. TheExpand
Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin
TLDR
The present structure presents a novel target-recognition mode of calmodulin and provides insight into the structural basis of the flexible interaction module of MARCKS. Expand
Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex.
The crystal structure of calcium-bound calmodulin (Ca(2+)-CaM) bound to a peptide analog of the CaM-binding region of chicken smooth muscle myosin light chain kinase has been determined and refinedExpand
NMR studies of caldesmon-calmodulin interactions.
TLDR
Both CaM-binding domains of CaD can bind simultaneously to the two hydrophobic regions of CaM, demonstrating the ability of these domains to regulate smooth muscle contraction. Expand
...
1
2
3
4
5
...