Two novel sub-domains within the cargo-binding domain of myosin V.
Natasha Pashkova (1), Natalie L. Catlett (1), Jennifer L. Novak (1), Robert E. Cohen (1), Guanming Wu (2), Renne Lu (2), Lois S. Weisman (1)
(1) Department of Biochemistry, University of Iowa, 51 Newton Road, Iowa City, IA, 52242, USA;
(2) Boston Biomedical Research Institute, Watertown, MA, 02472, USA
Myosin V motors function in relatively long-range movement on actin filaments. These motors are ubiquitously found in all eukaryotes. The yeast myosin V, Myo2p moves at least five types of cargoes including the vacuole and secretory vesicles. Attachment of Myo2p to its cargoes occurs through its carboxyl terminal globular tail domain. Previously, the globular tail had been viewed as a single functional entity. Here we show that this domain contains two distinct structural sub-domains I and II with distinct functions. Sub-domain I contains a vacuole-specific region, whereas sub-domain II contains a secretory vesicle-specific region. Biochemical and genetic analyses demonstrate that sub-domain I tightly associates with sub-domain II and that this interaction does not require additional proteins. Importantly, although neither sub-domain alone is functional, simultaneous expression of separate sub-domains I and II produces a functional complex in vivo and recapitulates phenotypes caused by over-expression of the full-length globular tail. Similarly, simultaneous expression enables the complex to associate with proteins that bind to the full-length Myo2p globular tail. It is likely that this direct interaction between two sub-domains is of physiological significance and may coordinate Myo2p association with distinct cargoes.
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