The evolving model of calmodulin structure,function and activation

Finn, Bryan E.; Forsén, Sture

doi:10.1016/s0969-2126(01)00130-7

Cited by 86 publications

(71 citation statements)

References 27 publications

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“…The mutations produced here resulted in relatively small ⍀ values, compared with those in Hidalgo and MacKinnon (25). One might predict that the inherent flexibility of CaM and the plasticity of its extensive hydrophobic interactions with varying targets (16,19,(33)(34)(35) contributed to the differing results, because the scorpion toxin-potassium channel system studied in Ref. 25 is characterized by a rigid, inflexible binding interface that is dominated by electrostatic interactions.…”

Section: Thermodynamic Mutant Cycle-based Analysis Of Off-rates In Highmentioning

confidence: 85%

Molecular Characterization of Calmodulin Trapping by Calcium/Calmodulin-dependent Protein Kinase II

Singla

Hudmon

Goldberg

et al. 2001

Journal of Biological Chemistry

100

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Section: Thermodynamic Mutant Cycle-based Analysis Of Off-rates In Highmentioning

confidence: 85%

Molecular Characterization of Calmodulin Trapping by Calcium/Calmodulin-dependent Protein Kinase II

Singla

Hudmon

Goldberg

et al. 2001

Journal of Biological Chemistry

100

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“…Calmodulin (CaM) is a universal eukaryotic Ca 2+ -sensing messenger protein that has been studied extensively by a large number of different biophysical methods (56). Ca…”

Section: Interplay Between Conformational Selection and Induced Fitmentioning

confidence: 99%

NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers

Sekhar

Kay

2013

Proc. Natl. Acad. Sci. U.S.A.

233

202

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The importance of dynamics to biomolecular function is becoming increasingly clear. A description of the structure-function relationship must, therefore, include the role of motion, requiring a shift in paradigm from focus on a single static 3D picture to one where a given biomolecule is considered in terms of an ensemble of interconverting conformers, each with potentially diverse activities. In this Perspective, we describe how recent developments in solution NMR spectroscopy facilitate atomic resolution studies of sparsely populated, transiently formed biomolecular conformations that exchange with the native state. Examples of how this methodology is applied to protein folding and misfolding, ligand binding, and molecular recognition are provided as a means of illustrating both the power of the new techniques and the significant roles that conformationally excited protein states play in biology.energy landscape | transiently and sparsely populated biomolecular states | invisible states | structure-function paradigmThe field of structural biology emerged from seminal X-ray diffraction studies of biomolecules such as DNA (1), myoglobin (2), hemoglobin (3), and lysozyme (4) that were carried out over 50 years ago. Since these landmark investigations, our knowledge of the relation between structure and function has greatly expanded, driven by significant improvements in both experimental and computational approaches and, of course, by the exponential increase in the number of structures that are now available. Despite tremendous advances, structural biology remains largely focused on studies of the lowest-energy conformational states of biomolecules, and although there are notable exceptions (5), the end game often remains the determination of a single static 3D structure that is then used as a starting point for understanding molecular function. It is becoming increasingly clear, however, that this narrow approach is not sufficient and that a description of molecular structure must take into account conformational fluctuations that can occur over a broad range of both time and length scales.The conformational space that can be explored by a given biomolecule is usually explained by invoking the concept of an energy landscape (6), a multidimensional hypersurface that governs the thermodynamics and kinetics of conformational transitions (7,8). Because biomolecular stability is dictated by the sum of a large number of attractive and repulsive interactions of similar strength, the resultant free-energy landscape is rugged (9), with the global minimum in the surface thought to correspond to the native state of the biomolecule. In addition, there are often local minima that are separated from the global minimum by free-energy barriers that can be overcome by thermal fluctuations. These low-lying conformationally excited states have remained elusive to quantitative investigation because their sparse population and transient nature complicates their study by conventional structural biology techniques that are so powerfu...

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“…The signalling role of calmodulin is intimately connected with the prevailing intracellular concentration of free Ca 21 ions. In the insect CNS, calmodulin is involved in nitric oxide (NO) synthesis [27][28][29]. NO is generated in neurones by Ca 21 /calmodulin-activated nitric oxide synthase (NOs), which catalyses the conversion of L-arginine and oxygen to NO and citrulline (Table 2).…”

Section: Signallingmentioning

confidence: 99%

Malaria Plasmodium agent induces alteration in the head proteome of their Anopheles mosquito host

et al. 2007

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Despite increasing evidence of behavioural manipulation of their vectors by pathogens, the underlying mechanisms causing infected vectors to act in ways that benefit pathogen transmission remain enigmatic in most cases. Here, 2-D DIGE coupled with MS were employed to analyse and compare the head proteome of mosquitoes (Anopheles gambiae sensu stricto (Giles)) infected with the malarial parasite (Plasmodium berghei) with that of uninfected mosquitoes. This approach detected altered levels of 12 protein spots in the head of mosquitoes infected with sporozoites. These proteins were subsequently identified using MS and functionally classified as belonging to metabolic, synaptic, molecular chaperone, signalling, and cytoskeletal groups. Our results indicate an altered energy metabolism in the head of sporozoite-infected mosquitoes. Some of the up-/down-regulated proteins identified, such as synapse-associated protein, 14-3-3 protein and calmodulin, have previously been shown to play critical roles in the CNS of both invertebrates and vertebrates. Furthermore, a heat shock response (HSP 20) and a variation of cytoarchitecture (tropomyosins) have been shown. Discovery of these proteins sheds light on potential molecular mechanisms that underlie behavioural modifications and offers new insights into the study of intimate interactions between Plasmodium and its Anopheles vector.

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The evolving model of calmodulin structure,function and activation

Abstract: Recent high-resolution crystal and solution structures have answered many long-standing questions about calmodulin and its various conformational states. However, there is still much to learn.

Cited by 86 publications

References 27 publications

Molecular Characterization of Calmodulin Trapping by Calcium/Calmodulin-dependent Protein Kinase II

Molecular Characterization of Calmodulin Trapping by Calcium/Calmodulin-dependent Protein Kinase II

NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers

Malaria Plasmodium agent induces alteration in the head proteome of their Anopheles mosquito host

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