Structure of the light chain-binding domain of myosin V

Terrak, Mohammed; Rębowski, Grzegorz; Lu, Renne Chen; Grabarek, Zenon; Domínguez, Roberto

doi:10.1073/pnas.0503899102

Cited by 60 publications

(125 citation statements)

References 47 publications

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“…By contrast, a ''straight-legged'' model was favored, based on FIONA analysis of processively walking myosin V (30). This latter observation is consistent with the crystal structure of the second and third IQ motifs from yeast myosin V with bound light chains (MLC1p), which showed a straight helix, and few interactions between light chains, despite a 25-aa spacing (27).…”

Section: The Semi-open Lobe Conformation and Its Specificity Of Recogsupporting

confidence: 49%

“…The site showing the most significant deviation from the consensus sequence is IQ6 (IQxxxRGxxxR is replaced by IQxxxRRxxxK), but this may not affect calcium sensitivity. It has been shown that the presence of a bulky side chain at position 7 and/or the absence of a positively charged residue at position 11 causes the N-lobe of CaM (or a specific light chain) to be in an unusual extended conformation that does not interact with the IQ motif (27). Such unbound N-lobes have been proposed to engage in protein-protein interactions.…”

Section: The Semi-open Lobe Conformation and Its Specificity Of Recogmentioning

confidence: 99%

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Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features

Houdusse

Gaucher

Krementsova

et al. 2006

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

132

216

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Section: The Semi-open Lobe Conformation and Its Specificity Of Recogsupporting

confidence: 49%

Section: The Semi-open Lobe Conformation and Its Specificity Of Recogmentioning

confidence: 99%

Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features

Houdusse

Gaucher

Krementsova

et al. 2006

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

132

216

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“…Alternatively, Ca 2ϩ -induced activation is initiated from the CaM in IQ2 and transduced to the CaM in IQ1 through interaction between these CaMs as shown in the crystal structure of light chain-binding domain of myosin V (29,31). It appears that activation of ATPase activity of myosin Va by high Ca 2ϩ is correlated with Ca 2ϩ -induced dissociation of CaM from a single specific IQ motif (32).…”

Section: Mechanism For Inhibition Of the Motor Domain Atpase By The Gtdmentioning

confidence: 99%

The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va

Li¹,

Jung

Wang³

et al. 2008

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

112

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Myosin Va is a well known processive motor involved in transport of organelles. A tail-inhibition model is generally accepted for the regulation of myosin Va: inhibited myosin Va is in a folded conformation such that the tail domain interacts with and inhibits myosin Va motor activity. Recent studies indicate that it is the C-terminal globular tail domain (GTD) that directly inhibits the motor activity of myosin Va. In the present study, we identified a conserved acidic residue in the motor domain (Asp-136) and two conserved basic residues in the GTD (Lys-1706 and Lys-1779) as critical residues for this regulation. Alanine mutations of these conserved charged residues not only abolished the inhibition of motor activity by the GTD but also prevented myosin Va from forming a folded conformation. We propose that Asp-136 forms ionic interactions with Lys-1706 and Lys-1779. This assignment locates the GTD-binding site in a pocket of the motor domain, formed by the N-terminal domain, converter, and the calmodulin in the first IQ motif. We propose that binding of the GTD to the motor domain prevents the movement of the converter/lever arm during ATP hydrolysis cycle, thus inhibiting the chemical cycle of the motor domain.

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“…The myosin-1C IQ motifs also lack the sequence features necessary to bind the N-lobe of apo-CaM. The glycine and arginine residues in the C-terminal GXXXR portion of conventional IQ motifs play important roles in binding the N-lobe of CaM, and both are missing in the myosin-1C IQ motifs (31,32).…”

Section: Discussionmentioning

confidence: 99%

“…The M1C-IQ1 and M1C-IQ2 motifs are each 18 residues in length and thus are considerably shorter than conventional IQ motifs that bind apo-CaM or CaM-related LCs, which typically include 23-25 amino acids (31). When the C-lobe of apo-CaM is modeled in place of MlcC on the M1C-IQ.1.2 fragment, there are substantial steric clashes between the two N-lobes that could preclude their binding to the IQ motifs (Fig.…”

Section: Discussionmentioning

confidence: 99%

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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Structure of the light chain-binding domain of myosin V

Cited by 60 publications

References 47 publications

Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features

Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features

The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va

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

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