Structure of the Small Dictyostelium discoideum Myosin Light Chain MlcB Provides Insights into MyoB IQ Motif Recognition

Liburd, Janine; Chitayat, Seth; Crawley, Scott W.; Munro, Kim; Miller, Emily; Denis, Chris M.; Spencer, Holly L.; Côté, Graham P.; Smith, Steven P.

doi:10.1074/jbc.m113.536532

Cited by 4 publications

(8 citation statements)

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“…Studies on CaMBPs involved in neurodegenerative disease, including Huntington, Batten's, and Alzheimer's disease, are already yielding valuable insights in this model microbe [65]. Dictyostelium has also proven its value in the study of IQ-mediated binding of a diversity of myosin light chain molecules [34,35,66]. Future work might focus on defining the functional residues involved in calcium-mediated CaM-binding as well as their role in mediating CaM-dependent events.…”

Section: Conclusion Comments and Speculationmentioning

confidence: 99%

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

O’Day

Taylor

Myre

2020

IJMS

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Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands are compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

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Section: Conclusion Comments and Speculationmentioning

confidence: 99%

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

O’Day

Taylor

Myre

2020

IJMS

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“… 182 In contrast, MlcB and MlcC are low molecular (8.3–8.6 kDa), single-lobe light chains. 185,186 MlcC EF-hands have lost the ability to bind Ca 2+ . 186 In contrast, MlcB can bind Ca 2+ and undergoes a Ca 2+ -dependent conformational change, however its tight, submicromolar affinity for the myosin-1B IQ motif is Ca 2+ -independent suggesting that structural plasticity is not critical for the MlcB:IQ interaction.…”

Section: Other Myosin Light Chains and Potential Light Chainsmentioning

confidence: 99%

Myosin light chains: Teaching old dogs new tricks

2014

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The myosin holoenzyme is a multimeric protein complex consisting of heavy chains and light chains. Myosin light chains are calmodulin family members which are crucially involved in the mechanoenzymatic function of the myosin holoenzyme. This review examines the diversity of light chains within the myosin superfamily, discusses interactions between the light chain and the myosin heavy chain as well as regulatory and structural functions of the light chain as a subunit of the myosin holoenzyme. It covers aspects of the myosin light chain in the localization of the myosin holoenzyme, protein-protein interactions and light chain binding to non-myosin binding partners. Finally, this review challenges the dogma that myosin regulatory and essential light chain exclusively associate with conventional myosin heavy chains while unconventional myosin heavy chains usually associate with calmodulin.

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“…The first EF-hand of MlcB is functional and binds Ca 2ϩ with a K d of 0.2 M, whereas both EF-hands of MlcC have lost the ability to bind Ca 2ϩ . NMR studies of MlcB show that it adopts a conformation in solution that differs from that of other Ca 2ϩ -binding proteins and that it binds to the myosin-1B IQ motif using a surface distinct from that employed by either the N-or C-terminal lobe of apo-CaM (26).…”

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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 …”

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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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Structure of the Small Dictyostelium discoideum Myosin Light Chain MlcB Provides Insights into MyoB IQ Motif Recognition

Cited by 4 publications

References 57 publications

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

Myosin light chains: Teaching old dogs new tricks

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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