The Globular Tail Domain of Myosin Va Functions as an Inhibitor of the Myosin Va Motor

Li, Xiangdong; Jung, Heinrich; Mabuchi, Katsuhide; Craig, Roger; Ikebe, Mitsuo

doi:10.1074/jbc.m602957200

Cited by 85 publications

(125 citation statements)

References 34 publications

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“…3, A and B; Supplemental Movies S1 and S3; data not shown). This result indicated that the XI-K tail-mediated suppression of Golgi trafficking did not require IQ or coiled-coil motifs and was likely dependent on interference with cargo binding rather than tail-mediated inhibition of the motor domain given that the latter tail activity was shown to require the coiled-coil region (Li et al, 2006).…”

Section: Isolation Of Myosin Cdnas From N Benthamiana and Phylogenetmentioning

confidence: 69%

Myosin XI-K Is Required for Rapid Trafficking of Golgi Stacks, Peroxisomes, and Mitochondria in Leaf Cells of Nicotiana benthamiana

et al. 2008

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A prominent feature of plant cells is the rapid, incessant movement of the organelles traditionally defined as cytoplasmic streaming and attributed to actomyosin motility. We sequenced six complete Nicotiana benthamiana cDNAs that encode class XI and class VIII myosins. Phylogenetic analysis indicates that these two classes of myosins diverged prior to the radiation of green algae and land plants from a common ancestor and that the common ancestor of land plants likely possessed at least seven myosins. We further report here that movement of Golgi stacks, mitochondria, and peroxisomes in the leaf cells of N. benthamiana is mediated mainly by myosin XI-K. Suppression of myosin XI-K function using dominant negative inhibition or RNA interference dramatically reduced movement of each of these organelles. When similar approaches were used to inhibit functions of myosin XI-2 or XI-F, only moderate to marginal effects were observed. Organelle trafficking was virtually unaffected in response to inhibition of each of the three class VIII myosins. Interestingly, none of the tested six myosins appears to be involved in light-induced movements of chloroplasts. Taken together, these data strongly suggest that myosin XI-K has a major role in trafficking of Golgi stacks, mitochondria, and peroxisomes, whereas myosins XI-2 and XI-F might perform accessory functions in this process. In addition, our analysis of thousands of individual organelles revealed independent movement patterns for Golgi stacks, mitochondria, and peroxisomes, indicating that the notion of coordinated cytoplasmic streaming is not generally applicable to higher plants.

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Section: Isolation Of Myosin Cdnas From N Benthamiana and Phylogenetmentioning

confidence: 69%

Myosin XI-K Is Required for Rapid Trafficking of Golgi Stacks, Peroxisomes, and Mitochondria in Leaf Cells of Nicotiana benthamiana

et al. 2008

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confidence: 94%

“…We found that strong inhibition of motor activity by the GTD requires not only the two-headed structure, but also the presence of an intact first long coiled-coil segment of the tail (9). Based on these findings, we proposed that the GTD simultaneously binds to the motor domain and the C terminus of the first long coiled-coil segment of the tail, thus forming a triangular conformation (9). However, the precise interaction between the GTD and the motor domain and thus the mechanism of inhibition remained unclear.…”

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confidence: 98%

“…Later, it was found that the GTD directly inhibits the activity of the motor domain of myosin-Va: Myosin-Va HMM is inhibited and folded by exogenous GTD (9,10). We found that strong inhibition of motor activity by the GTD requires not only the two-headed structure, but also the presence of an intact first long coiled-coil segment of the tail (9). Based on these findings, we proposed that the GTD simultaneously binds to the motor domain and the C terminus of the first long coiled-coil segment of the tail, thus forming a triangular conformation (9).…”

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confidence: 99%

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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.

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109

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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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“…However, if all the coiled-coil domains and the inter-coiled-coil regions were in an extended conformation, the length of the neck domains would not allow the heads to reach the GTDs. Indeed, the GTDs were shown to interact with the C-terminal part of the proximal coiled-coil region, and this interaction was proved to be necessary for the binding of the heads in the inactive conformation (68). It is obvious that the direction of the myosin 5a heavy chains must be totally reversed in this conformation to allow the GTDs to reach the proximal coiled-coil.…”

Section: Discussionmentioning

confidence: 99%

DYNLL2 Dynein Light Chain Binds to an Extended Linear Motif of Myosin 5a Tail That Has Structural Plasticity

Bodor¹,

Radnai²,

Hetényi

et al. 2014

Biochemistry

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LC8 dynein light chains (DYNLL) are conserved homodimeric eukaryotic hub proteins that participate in diverse cellular processes. Among the binding partners of DYNLL2, myosin 5a (myo5a) is a motor protein involved in cargo transport. Here we provide a profound characterization of the DYNLL2 binding motif of myo5a in free and DYNLL2 bound form by using NMR spectroscopy, Xray crystallography and molecular dynamics simulations. In the free form the DYNLL2 binding region, located in an intrinsically disordered domain of the myo5a tail, has a nascent helical character. The motif becomes structured and folds into a β-strand upon binding to DYNLL2. Despite all differences of the myo5a sequence from the consensus binding motif, it accommodates into the same DYNLL2 binding groove as all other partners do. Interestingly, while the core motif shows similar interaction pattern in the binding groove as seen inother complexes, the flanking residues make several additional contacts, thereby lengthening the binding motif. The N-terminal extension folds back and partially blocks the free edge of the β-sheet formed by the binding motif itself. The C-terminal extension contacts the dimer interface and interacts with symmetry related residues of the second myo5a peptide. The involvement of flanking residues of the core binding site of myo5a could modify the quaternary structure of the full-length myo5a and affect its biological functions. The presented structural data widen our understanding of the diverse partner recognition of DYNLL proteins and provide an example of a Janus-faced linear motif. 4The LC8 dynein light chains were originally described as the smallest subunit of the microtubuleassociated cytoplasmic dynein motor complex.They show a highly conserved amino acid sequence throughout evolution and they were later shown to bind to more than 70 other proteins involved in various biological processes, therefore they are now considered hub proteins (1, 2).Vertebrates contain two closely related LC8 paralogs, DYNLL1 and DYNLL2 with partially overlapping functions(1). Under physiological conditions LC8proteins arestable homodimers (3).Atomic resolution structureswere determined both for the apo and ligand-bound form using X-ray crystallographyand NMR spectroscopy (4-6). Five β-strands make up two core β-sheets; one sideof each sheet is flanked by two α-helices, and the otherside forms the dimer interface. The β3-strand of one subunit pairs to theβ2"-strandof the other subunitin an antiparallel mode; and the dimer is stabilized by interface contacts through hydrophobic interactions and side chain H-bonds. Two equivalent grooves are formed and they represent the target binding pockets of the dimer. The primary transcript of the human MYO5A geneis processed by alternative splicing (13). Three exons 5 within the tail domain (B, D, and F) are expressed in a cell type-specific manner; the predominant melanocyte-and brain-specific isoforms contains exons D, F, and exon B, respectively (13). The exon pattern of myo5a tail lik...

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The Globular Tail Domain of Myosin Va Functions as an Inhibitor of the Myosin Va Motor

Cited by 85 publications

References 34 publications

Myosin XI-K Is Required for Rapid Trafficking of Golgi Stacks, Peroxisomes, and Mitochondria in Leaf Cells of Nicotiana benthamiana

Myosin XI-K Is Required for Rapid Trafficking of Golgi Stacks, Peroxisomes, and Mitochondria in Leaf Cells of Nicotiana benthamiana

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

DYNLL2 Dynein Light Chain Binds to an Extended Linear Motif of Myosin 5a Tail That Has Structural Plasticity

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