Myosin XVIIIa has a large predicted coiled-coil forming sequence, but the structure of the myosin has not been examined on a single molecule level. We expressed full length myosin XVIIIa from mouse and showed that it has a long tail similar to that of myosin II. We are examining whether this tail can form filaments. We are also studying myosin XVIIIa from Drosophila. We have been examining two isoforms of this myosin that differ in their amino-terminal sequences. One isoform contains a PDZ domain at the N-terminus while the other does not. Neither isoform of this myosin has an actin activated MgATPase, and or binds nucleotide. Both bind to actin in an ATP-independent manner with an affinity of around 1 uM. Interestingly, there is a an equilibrium between two states of the myosin, one that is competent to bind actin and one that is not. Optical trapping experiments demonstrate that the myosin can interact with actin, but there is no net displacement of actin resulting from these interactions. We have also begun expressing myosin IXb and are studying its interaction with actin.

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National Heart, Lung, and Blood Institute
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Gardini, Lucia; Heissler, Sarah M; Arbore, Claudia et al. (2018) Dissecting myosin-5B mechanosensitivity and calcium regulation at the single molecule level. Nat Commun 9:2844
Zheng, Wei; Wu, Yicong; Winter, Peter et al. (2017) Adaptive optics improves multiphoton super-resolution imaging. Nat Methods 14:869-872
Heissler, Sarah M; Chinthalapudi, Krishna; Sellers, James R (2017) Kinetic signatures of myosin-5B, the motor involved in microvillus inclusion disease. J Biol Chem 292:18372-18385
Heissler, Sarah M; Sellers, James R (2016) Various Themes of Myosin Regulation. J Mol Biol 428:1927-46
Martin, Andreas; Berger, James M; Sellers, James R et al. (2016) Mechanisms and Functional Diversity of Macromolecular Remodeling by ATP-Dependent Motors. J Mol Biol 428:1819-21
Heissler, Sarah M; Sellers, James R (2016) Kinetic Adaptations of Myosins for Their Diverse Cellular Functions. Traffic 17:839-59
Kengyel, András; Bécsi, Bálint; Kónya, Zoltán et al. (2015) Ankyrin domain of myosin 16 influences motor function and decreases protein phosphatase catalytic activity. Eur Biophys J 44:207-18
Bond, Lisa M; Sellers, James R; McKerracher, Lisa (2015) Rho kinase as a target for cerebral vascular disorders. Future Med Chem 7:1039-53
Andrecka, Joanna; Ortega Arroyo, Jaime; Takagi, Yasuharu et al. (2015) Structural dynamics of myosin 5 during processive motion revealed by interferometric scattering microscopy. Elife 4:
Ortega Arroyo, J; Andrecka, J; Spillane, K M et al. (2014) Label-free, all-optical detection, imaging, and tracking of a single protein. Nano Lett 14:2065-70

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