Identification of Calmodulin and MlcC as Light Chains for <i>Dictyostelium</i> Myosin-I Isozymes

Crawley, Scott W.; Liburd, Janine; Shaw, Kristopher; Jung, Yoojin; Smith, Steven P.; Côté, Graham P.

doi:10.1021/bi2007178

Cited by 12 publications

(25 citation statements)

References 53 publications

(115 reference statements)

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“…Dictyostelium MlcC is an atypical small light chain composed of two EF-hand motifs, neither of which is able to bind Ca 2ϩ (23). MlcC functions as the light chain for myosin-1C, a long-tailed class-1 myosin.…”

Section: Discussionmentioning

confidence: 99%

“…The first two IQ motifs of myosin-1C are divergent from the consensus IQ sequences in that they are 18 amino acid residues in length, and the conserved glutamine is substituted for a lysine and is specifically recognized by the LC MlcC (23). The identity of the LC that binds IQ3 of myosin-1C is not currently known.MlcB and MlcC consist of two helix-loop-helix EF-hand motifs connected by a short linker sequence, and particularly relevant to the biological function are monomers in solution (23,25,26 …”

mentioning

confidence: 99%

“…MlcB and MlcC consist of two helix-loop-helix EF-hand motifs connected by a short linker sequence, and particularly relevant to the biological function are monomers in solution (23,25,26 …”

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confidence: 99%

“…A variety of different LCs are associated with the Dictyostelium myosin-1 isozymes. Myosin-1A and myosin-1E use CaM as a LC, whereas myosin-1D binds MlcD, a 17-kDa CaM-related protein that lacks the ability to bind Ca 2ϩ (23,24). The LCBDs of myosin-1B and myosin-1C contain one and three IQ motifs, respectively, with the IQ motif of the former displaying specific binding to the small (i.e.…”

mentioning

confidence: 99%

“…ϳ8.5 kDa) LC MlcB (25). The first two IQ motifs of myosin-1C are divergent from the consensus IQ sequences in that they are 18 amino acid residues in length, and the conserved glutamine is substituted for a lysine and is specifically recognized by the LC MlcC (23). The identity of the LC that binds IQ3 of myosin-1C is not currently known.…”

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confidence: 99%

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Structure of the Single-lobe Myosin Light Chain C in Complex with the Light Chain-binding Domains of Myosin-1C Provides Insights into Divergent IQ Motif Recognition

Langelaan¹,

Liburd²,

Yang

et al. 2016

Journal of Biological Chemistry

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Myosin light chains are key regulators of class 1 myosins and typically comprise two domains, with calmodulin being the archetypal example. They bind IQ motifs within the myosin neck region and amplify conformational changes in the motor domain. A single lobe light chain, myosin light chain C (MlcC), was recently identified and shown to specifically bind to two sequentially divergent IQ motifs of the Dictyostelium myosin-1C. To provide a molecular basis of this interaction, the structures of apo-MlcC and a 2:1 MlcC⅐myosin-1C neck complex were determined. The two non-functional EF-hand motifs of MlcC pack together to form a globular four-helix bundle that opens up to expose a central hydrophobic groove, which interacts with the N-terminal portion of the divergent IQ1 and IQ2 motifs. The N-and C-terminal regions of MlcC make critical contacts that contribute to its specific interactions with the myosin-1C divergent IQ motifs, which are contacts that deviate from the traditional mode of calmodulin-IQ recognition.The class 1 myosins (myosin-1) are a widely expressed family of single-headed, non-filament-forming, membrane-binding myosins (1-3). The myosin-1 heavy chain consists of a highly conserved N-terminal motor domain with sites for binding actin and for ATP hydrolysis, a light chain-binding domain (LCBD) 5 that acts as the motor's lever arm, and a C-terminal tail. The myosin-1 tail contains a tail homology 1 (TH1) domain that interacts with acidic phospholipids and, in some cases, also contains a glycine-and proline-rich TH2 domain that binds filamentous actin and an Src homology 3 domain that forms complexes with proteins that stimulate actin filament assembly (4 -10). Myosin-1 is able to cross-link the plasma membrane to the underlying actin cytoskeleton and plays a direct role in the control of cortical and membrane tension (11,12). These motor proteins can also drive vesicle trafficking, pseudopod retraction, and the uptake of particles and fluids by phagocytosis and micropinocytosis (13-16).The myosin-1 LCBD includes one or more IQ motifs, which are ␣-helical sequences between 18 and 25 residues in length that terminate with a loosely conserved IQXXXRGXXXR consensus sequence (17, 18). IQ motifs bind calmodulin (CaM) or CaM-related light chains (LCs) in the absence of Ca 2ϩ . The LCs stabilize the ␣-helical structure of the LCBD, allowing it to function as a rigid swinging lever arm to amplify ATP-dependent conformational changes that originate within the motor domain (19). The LCs are also important regulatory sites that interact with the motor domain to influence mechanochemical properties such as step size, motility rate, and force sensing (1,20,21).The social amoeba Dictyostelium discoideum has been used extensively to study myosin-1 structure, function, and regulation. The seven Dictyostelium myosin-1 isozymes include three with short tails that contain only a TH1 domain (myosin-1A, -1E, and -1F), three with long tails that have TH1, TH2, and Src homology 3 domains (myosin-1B, -1C, and -1D), and one ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…MlcB and MlcC consist of two helix-loop-helix EF-hand motifs connected by a short linker sequence, and particularly relevant to the biological function are monomers in solution (23,25,26 …”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structure of the Single-lobe Myosin Light Chain C in Complex with the Light Chain-binding Domains of Myosin-1C Provides Insights into Divergent IQ Motif Recognition

Langelaan¹,

Liburd²,

Yang

et al. 2016

Journal of Biological Chemistry

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Selective localization of myosin‐I proteins in macropinosomes and actin waves

et al. 2016

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Class I myosins are widely expressed with roles in endocytosis and cell migration in a variety of cell types. Dictyostelium express multiple myosin Is, including three short-tailed (Myo1A, Myo1E, Myo1F) and three long-tailed (Myo1B, Myo1C, Myo1D). Here we report the molecular basis of the specific localizations of short-tailed Myo1A, Myo1E and Myo1F compared to our previously determined localization of long-tailed Myo1B. Myo1A and Myo1B have common and unique localizations consistent with the various features of their tail region; specifically the BH sites in their tails are required for their association with the plasma membrane and heads are sufficient for relocalization to the front of polarized cells. Myo1A does not localize to actin waves and macropinocytic protrusions, in agreement with the absence of a tail region which is required for these localizations of Myo1B. However, in spite of the overall similarity of their domain structures, the cellular distributions of Myo1E and Myo1F are quite different from Myo1A. Myo1E and Myo1F, but not Myo1A, are associated with macropinocytic cups and actin waves. The localizations of Myo1E and Myo1F in macropinocytic structures and actin waves differ from the localization of Myo1B. Myo1B colocalizes with F-actin in the actin waves and at the tips of mature macropinocytic cups whereas Myo1E and Myo1F are in the interior of actin waves and along the entire surface of macropinocytic cups. Our results point to different mechanisms of targeting of short- and long-tailed myosin Is, and are consistent with these myosins having both shared and divergent cellular functions.

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Myosin B of Plasmodium falciparum (PfMyoB): in silico prediction of its three-dimensional structure and its possible interaction with MTIP

et al. 2017

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The mobility and invasion strategy of Plasmodium falciparum is governed by a protein complex known as the glideosome, which contains an actin-myosin motor. It has been shown that myosin A of the parasite (PfMyoA) is the myosin of the glideosome, and the interaction of PfMyoA with myosin tail domain interacting protein (MTIP) determines its correct location and its ability to function in the complex. Because PfMyoA and myosin B of P. falciparum (PfMyoB) share high sequence identity, are both small proteins without a tail domain, belong to the class XIV myosins, and are expressed in late schizonts and merozoites, we suspect that these myosins may have similar or redundant functions. Therefore, this work examined the structural similarity between PfMyoA and PfMyoB and performed a molecular docking between PfMyoB and MTIP. Three-dimensional (3D) models obtained for PfMyoA and PfMyoB achieved high scores in the structural validation programs used, and their superimposition revealed high structural similarity, supporting the hypothesis of possible similar functions for these two proteins. The 3D interaction models obtained and energy values found suggested that interaction between PfMyoB and MTIP is possible. Given the apparent abundance of PfMyoA relative to PfMyoB in the parasite, we believe that the interaction between PfMyoB and MTIP would only be detectable in specific cellular environments because under normal circumstances, it would be masked by the interaction between PfMyoA and MTIP.

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Identification of Calmodulin and MlcC as Light Chains for Dictyostelium Myosin-I Isozymes

Cited by 12 publications

References 53 publications

Structure of the Single-lobe Myosin Light Chain C in Complex with the Light Chain-binding Domains of Myosin-1C Provides Insights into Divergent IQ Motif Recognition

Structure of the Single-lobe Myosin Light Chain C in Complex with the Light Chain-binding Domains of Myosin-1C Provides Insights into Divergent IQ Motif Recognition

Selective localization of myosin‐I proteins in macropinosomes and actin waves

Myosin B of Plasmodium falciparum (PfMyoB): in silico prediction of its three-dimensional structure and its possible interaction with MTIP

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