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

Li, Xiangdong; Jung, Heinrich; Wang, Qizhi; Ikebe, Reiko; Craig, Roger; Ikebe, Mitsuo

doi:10.1073/pnas.0709741105

Cited by 71 publications

(117 citation statements)

References 37 publications

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“…Conserved basic residues (K1706 and K1779) found on the tip of the SD-2 H7-H8 loop and H11 helices are essential for this regulation (21). Whereas this region is conserved in vertebrate Myo5 and yeast Myo2p, it is not in Myo4p (18).…”

Section: Resultsmentioning

confidence: 99%

“…Mutational analysis has shown that the SD-2 tip of the GTD interacts with the motor domain in the folded inhibited state (21). The general topology of the folded Myo5 conformation indicates that the SD-1 tips of the two GTDs in the folded Myo5 dimer might interact with each other and with the stalk.…”

Section: Structural Recognition Of the Mlph By An Isoform-specific Bimentioning

confidence: 99%

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Structural basis of myosin V Rab GTPase-dependent cargo recognition

Pylypenko

Attanda

Gauquelin

et al. 2013

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

108

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Specific recognition of the cargo that molecular motors transport or tether to cytoskeleton tracks allows them to perform precise cellular functions at particular times and positions in cells. However, very little is known about how evolution has favored conservation of functions for some isoforms, while also allowing for the generation of new recognition sites and specialized cellular functions. Here we present several crystal structures of the myosin Va or the myosin Vb globular tail domain (GTD) that gives insights into how the motor is linked to the recycling membrane compartments via Rab11 or to the melanosome membrane via recognition of the melanophilin adaptor that binds to Rab27a. The structures illustrate how the Rab11-binding site has been conserved during evolution and how divergence at another site of the GTD allows more specific interactions such as the specific recognition of melanophilin by the myosin Va isoform. With atomic structural insights, these structures also show how either the partner or the GTD structural plasticity upon association is critical for selective recruitment of the motor.GTPases | DIL motif | Rab effector | intracellular traffic D irected movement is essential for life, and cytoskeletonbased motors generate mechanical force and motion to precisely organize the cell. Their coordinated actions allow them to play key roles in nearly every physiological process. Class V myosins (Myo5) and the related plant class XI myosins are a group of multifunctional actin-based nanomotors that have evolved from one of the three ancient myosin subfamilies (1). The motor domain and extended lever arm of these myosins is followed by a coiled coil dimerizing region and the C-terminal globular tail domain (GTD) that primarily plays a role in selective cargo recruitment. Little is known, however, about how this GTD sequence has evolved to serve both a role in regulation of the motor activity (2, 3) and specific recruitment of the motor, which is critical to control precisely in space and time when the motor is activated for different cellular functions.

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Section: Resultsmentioning

confidence: 99%

Section: Structural Recognition Of the Mlph By An Isoform-specific Bimentioning

confidence: 99%

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Pylypenko

Attanda

Gauquelin

et al. 2013

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

108

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“…The existence of the folded inhibited state of mammalian myosin V is supported by sedimentation analysis (Krementsov et al, 2004;Li et al, 2004;Wang et al, 2004), cryoelectron microscopy reconstruction (Liu et al, 2006;Thirumurugan et al, 2006), and ATPase activity assays (Li et al, 2008). Activation of the motor occurs after cargo receptor binding for MyoVa in vitro (Li et al, 2005;Sckolnick et al, 2013), as is the case for yeast myosin V in vivo (Donovan and Bretscher, 2012).…”

Section: Introductionmentioning

confidence: 91%

Head-to-tail regulation is critical for the in vivo function of myosin V

Donovan¹,

Bretscher²

2015

J Gen Physiol

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“…The recombinant baculovirus encoding the cDNA of Myo5 heavy chain was prepared as described previously (7,24). To prepare Myo5 proteins, Sf9 cells were co-infected with the recombinant baculovirus encoding Myo5 heavy chain and that encoding CaM and purified as described previously (7,24). The concentrationsofthepurifiedproteinsweredeterminedbyabsorbance at 280 nm using the following molar extinction coeffi- , Myo5c(5aIQ1)-HMM.…”

Section: Methodsmentioning

confidence: 99%

“…The GTD interacts with different cargo-binding proteins through distinct binding sites located on the surface of both subdomain I and II (12, 14, 15, 18 -20). On the other hand, bioinformatic analysis and biochemical characterization suggest that the head-binding site is located in subdomain II (7,12,22).…”

mentioning

confidence: 99%

Identification of the Isoform-specific Interactions between the Tail and the Head of Class V Myosin

Yao

Shen

et al. 2016

Journal of Biological Chemistry

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Vertebrates have three isoforms of class V myosin (Myo5), Myo5a, Myo5b, and Myo5c, which are involved in transport of multiple cargoes. It is well established that the motor functions of Myo5a and Myo5b are regulated by a tail inhibition mechanism. Here we found that the motor function of Myo5c was also inhibited by its globular tail domain (GTD), and this inhibition was abolished by high Ca 2؉ , indicating that the tail inhibition mechanism is conserved in vertebrate Myo5. Interestingly, we found that Myo5a-GTD and Myo5c-GTD were not interchangeable in terms of inhibition of motor function, indicating isoform-specific interactions between the GTD and the head of Myo5. To identify the isoform-specific interactions, we produced a number of Myo5 chimeras by swapping the corresponding regions of Myo5a and Myo5c. We found that Myo5a-GTD, with its H11-H12 loop being substituted with that of Myo5c, was able to inhibit the ATPase activity of Myo5c and that Myo5a-GTD was able to inhibit the ATPase activity of Myo5c-S1 and Myo5c-HMM only when their IQ1 motif was substituted with that of Myo5a. Those results indicate that the H11-H12 loop in the GTD and the IQ1 motif in the head dictate the isoformspecific interactions between the GTD and head of Myo5. Because the IQ1 motif is wrapped by calmodulin, whose conformation is influenced by the sequence of the IQ1 motif, we proposed that the calmodulin bound to the IQ1 motif interacts with the H11-H12 loop of the GTD in the inhibited state of Myo5.

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

Cited by 71 publications

References 37 publications

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Head-to-tail regulation is critical for the in vivo function of myosin V

Identification of the Isoform-specific Interactions between the Tail and the Head of Class V Myosin

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