PDBsum entry 2fcd

Cell cycle

PDB id: 2fcd

Contents

Protein chain

78 a.a.

References listed in PDB file

Key reference

Title

Structural basis for the interaction of the myosin light chain mlc1p with the myosin V myo2p iq motifs.

Authors

M.Pennestri, S.Melino, G.M.Contessa, E.C.Casavola, M.Paci, A.Ragnini-Wilson, D.O.Cicero.

Ref.

J Biol Chem, 2007, 282, 667-679. [DOI no: 10.1074/jbc.M607016200]

PubMed id

17074768

Abstract

Calmodulin, regulatory, and essential myosin light chain are evolutionary conserved proteins that, by binding to IQ motifs of target proteins, regulate essential intracellular processes among which are efficiency of secretory vesicles release at synapsis, intracellular signaling, and regulation of cell division. The yeast Saccharomyces cerevisiae calmodulin Cmd1 and the essential myosin light chain Mlc1p share the ability to interact with the class V myosin Myo2p and Myo4 and the class II myosin Myo1p. These myosins are required for vesicle, organelle, and mRNA transport, spindle orientation, and cytokinesis. We have used the budding yeast model system to study how calmodulin and essential myosin light chain selectively regulate class V myosin function. NMR structural analysis of uncomplexed Mlc1p and interaction studies with the first three IQ motifs of Myo2p show that the structural similarities between Mlc1p and the other members of the EF-hand superfamily of calmodulin-like proteins are mainly restricted to the C-lobe of these proteins. The N-lobe of Mlc1p presents a significantly compact and stable structure that is maintained both in the free and complexed states. The Mlc1p N-lobe interacts with the IQ motif in a manner that is regulated both by the IQ motifs sequence as well as by light chain structural features. These characteristic allows a distinctive interaction of Mlc1p with the first IQ motif of Myo2p when compared with calmodulin. This finding gives us a novel view of how calmodulin and essential light chain, through a differential binding to IQ1 of class V myosin motor, regulate this activity during vegetative growth and cytokinesis.

Figure 2.
FIGURE 2. An N-domain structure comparison between Mlc1p (PDB entry 1M46 (10), green) and apoCaM (PDB entry 1CFD, red). Structure superposition was performed considering backbone atoms belonging to residues of the four helices: 5-14, 26-32, 40-48, and 61-68 (Mlc1p) and 10-19, 31-37, 45-53, and 65-72 (apoCaM). Highlighted are residues that confer special structural features to Mlc1p; Leu-75, that is added to the hydrophobic core of the N-lobe, and Thr-78 and Asn-37, which interact through hydrogen bonds. Asn-37 is a key residue for the regulation of the interaction between the N-lobe and IQ-spanning peptides. B, chemical shift index for C and ^3J[HNH ]measured for helix D and helix D'. C, strips from ^13C- and ^15N-edited NOESY spectra showing the interaction between Thr-78 and Asn-37 and several NOEs from Leu-75 methyl groups.

Figure 7.
FIGURE 7. Superposition of the C domains belonging to different light chains. Mlc1p C domain is shown in the three figures in green. A, B, and C show the superposition with apoCaM (1CFD), Cmd1 (1LKJ) and Cdc4p (1GGW), respectively. Residues used for the superposition were 83-112, 135-146 (Mlc1p), 82-111, 134-145 (apoCaM), 82-111, 133-144 (Cmd1), and 76-105, 126-137 (Cdc4p).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 667-679) copyright 2007.