Calmodulin structure

Finn, B.E., Forsen, S. The evolving model of calmodulin structure, function and activation. Structure 3 7-11, 1995. 

Calmodulin Structure by X-Ray and NMR. Babu and co-workers published the first X-ray crystallographic structure of Ca " -saturated mammalian calmodulin in 1986 (PDB ascension number 3CLN). As can be seen in Figure 6.21, the molecule is dumbbell-shaped, with an overall length of 65 A. There are two two-EF-hand domains or lobes— N-terminal, residues 5-73 and C-terminal, residues 74-148—connected by a central seven-turn a-helix. The center part of the connecting helix is unwound between residues asp78 and... 

Calmodulin Structure (Source) Method Angle (°) A-B (I-II) Angle (°) C-D (III-IV) Angle (°) E-F (V-VI) Angle (°) G-H (VII-VIII) PDB Entry (Reference Number)... 

R. Mannhold (1984). Calmodulin—structure, function and drug action. Drugs Euture 9 677-691. 

With the help of NMR measurement, it has been shown that the Ca2+/calmodulin complex has a flexible structure. Flexibility is probably of great importance for the function of Ca2+/calmodulin. Structural information on Ca2+/calmodulin bound to substrates is only available for peptides derived from target proteins. In the complex with peptide substrates (Fig. 6.13), Ca2+/calmodulin has a collapsed structure in which the two globular domains are much closer together than in free Ca2+/calmodulin, and it wraps around and sequesters the helical calmodulin-binding peptides. 

For those interested in the pharmacology of calmodulin antagonists or physicochemical studies on calmodulin structure, Vincenzi (1981) and Krebs (1981) are suggested. Reviews that include substantial sections on the adenylate cyclase-phosphodiesterase systems and calmodulin or on calmodulin-dependent protein phosphorylations can be found in Cheung (1981), Brostrom and Wolf (1981), and Stoclet (1981). 

Calmodulin is a calcium-dependent protein that modulates other protein activity via protein interactions. The overall structure of calmodulin is variable, and is modulated by calcium. An NMR structure of calmodulin is foimd in PDB record 2BBN, complexed with a peptide. How many models are in this structure Find other calmodulin structures from the PDB site, and inspect them using RasMol. How many gross, unique conformations can this protein be foimd in Where, in terms of secondary structure, is the site of the largest structural change ... 

One of these motifs, called the helix-turn-helix motif, is specific for DNA binding and is described in detail in Chapters 8 and 9. The second motif is specific for calcium binding and is present in parvalbumin, calmodulin, tro-ponin-C, and other proteins that bind calcium and thereby regulate cellular activities. This calcium-binding motif was first found in 1973 by Robert Kretsinger, University of Virginia, when he determined the structure of parvalbumin to 1.8 A resolution. 

The x-ray structure of free calmodulin was determined by the group of Charles Bugg, University of Alabama. It is a dumbbell-shaped molecule... 

Figure 6.21 Schematic diagram of the conformational changes of calmodulin upon peptide binding, (a) In the free form the calmodulin molecule is dumhhell-shaped comprising two domains (red and green), each having two EF hands with bound calcium (yellow), (b) In the form with bound peptides (blue) the a helix linker has been broken, the two ends of the molecule are close together and they form a compact globular complex. The internal structure of each domain is essentially unchanged. The hound peptide binds as an a helix.

Babu, Y.S., et al. Three-dimensional structure of calmodulin. Nature 315 37-40, 1985. 

Ikura, M., et al. Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256 632-638, 1992. 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

The Ca2+-binding subunit TN-C is homologous to calmodulin with four EF-hands. In contrast to calmodulin, which is ubiquitously expressed in multicellular eukaryotic organisms and interacts with many targets, troponin specifically regulates muscle contraction. There are some structural differences between Troponin C in skeletal and cardiac muscles reflecting their physiological differences. 

Centrins are calmodulin-like proteins that have an important function in the organization and duplication of microtubules. Like CaM, centrin is also comprized of two structurally independent globular domains connected by a flexible tether, and each domain is... 

In addition to its effects on enzymes and ion transport, Ca /calmodulin regulates the activity of many structural elements in cells. These include the actin-myosin complex of smooth muscle, which is under (3-adrenergic control, and various microfilament-medi-ated processes in noncontractile cells, including cell motility, cell conformation changes, mitosis, granule release, and endocytosis. 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

The Ca transport ATPase of the surface membrane is a Ca -calmodulin-dependent enzyme of approximately 138-kDa mass that is structurally distinct from the sarcoplasmic reticulum Ca -ATPase, but shares with it some similarities in the mechanism of Ca translocation [2,3,34]. In both enzymes the Ca -dependent phosphorylation of an aspartyl-carboxyl-group by ATP leads to the formation of an acyl phosphate intermediate that provides the coupling between ATP hydrolysis and Ca translocation. 

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