High impact information on MLC1

• The crystal structures of Mlc1p bound to IQ2 and IQ4 of Myo2p differ dramatically [1].
• Mlc1p promotes septum closure during cytokinesis via the IQ motifs of the vesicle motor Myo2p [2].
• MLC1 (YGL106w) is an essential gene that exhibits haploinsufficiency [3].
• Our results suggest that Mlc1p is responsible for stabilizing this myosin by binding to the neck region [3].
• Essential myosin light chain as a target for caspase-3 in failing myocardium [4].

Biological context of MLC1

• Immunofluorescence staining shows that Mlc1p is localized to sites of polarized cell growth as well as the bud neck before and independently of Cyk1p [5].
• 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 [6].
• Mlc1p is also found at the incipient bud site in G(1) and the growing bud tip during S and G(2) phases of the cell cycle [7].
• Both proteins localize to the bud neck in mitosis although Mlc1p localisation precedes Iqg1p [7].
• The head domain is notable in that it contains a approximately 30 residue insert near the nucleotide binding pocket, and five potential calmodulin/myosin light chain binding sites at the head/tail junction [8].

Anatomical context of MLC1

• Myosin phosphatase, the key enzyme controlling myosin light chain dephosphorylation, regulates smooth muscle cell contraction [9].
• An unexpected result obtained during the course of these studies was the observation that myosin light chain kinases from smooth and skeletal muscle tissues can respond differently to mutations in calmodulin [10].
• Myosin light chain phosphorylation does not increase during yeast phagocytosis by macrophages [11].
• The endothelial cell Ca2+/calmodulin (CaM)-dependent myosin light chain kinase isoform (EC MLCK) is a multifunctional contractile effector involved in vascular barrier regulation, leukocyte diapedesis, apoptosis, and angiogenesis [12].

Associations of MLC1 with chemical compounds

• In the presence of both Ca(2+) and a peptide synthesized to mimic the CaM binding domain on myosin light chain kinase, MLCK-22p, the solution structures of these chimeric CaMs take a similar compact globular shape but their interactions are quite different [13].
• Electron-density maps for two of the complexes (Mlc1p-IQ4 and Mlc1p-IQ2,3) were obtained from multiple anomalous dispersion (MAD) experiments based on selenomethionine derivatives [14].
• Both calmodulins activated muscle myosin light chain kinase and pea NAD+ kinase in a Ca2+-dependent manner, and the activities were inhibited by trifluoperazine or chlorpromazine [15].
• These ameba gene segments were homologous to myosin light chain kinases, protein kinase C, phosphorylase b kinase, and kinases that regulate glucose repression in yeast and cell growth in mammalian cells [16].

Physical interactions of MLC1

• Mlc1p is also shown to interact with the class II conventional myosin (Myo1p) [7].

Other interactions of MLC1

• Reduced levels of MYO2 overcome the haploinsufficiency of MLC1 [3].
• We propose that Mlc1p/Myo2p interaction is stimulated by a signal that requires Sec2p and activation of Ypt32p [17].
• Mlc1p is a light chain for the unconventional myosin Myo2p in Saccharomyces cerevisiae [3].
• CONCLUSION: Dictyostelium contains thirteen myosins together with 6-8 MLCs (myosin light chain) to assist in a variety of actin-based processes in the cell [18].

Analytical, diagnostic and therapeutic context of MLC1

• This structure, combined with FRET distance measurements between probes in various CaM-IQ complexes, comparative sequence analysis, and the previously determined structures of Mlc1p-IQ2 and Mlc1p-IQ4, allowed building a model of the LCBD of myosin V [19].
• Crystallization, X-ray characterization and selenomethionine phasing of Mlc1p bound to IQ motifs from myosin V [14].

References