Structure of androcam supports specialized interactions with myosin VI

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dc.citation.firstpage13290
dc.citation.issueNumber33
dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.citation.lastpage13295
dc.citation.volumeNumber109
dc.contributor.authorJoshi, Mehul K.
dc.contributor.authorMoran, Sean
dc.contributor.authorBeckingham, Kathleen M.
dc.contributor.authorMacKenzie, Kevin R.
dc.date.accessioned2013-08-22T21:53:25Z
dc.date.available2013-08-22T21:53:25Z
dc.date.issued2012
dc.description.abstractAndrocam replaces calmodulin as a tissue-specific myosin VI light chain on the actin cones that mediate D. melanogaster spermatid individualization. We show that the androcam structure and its binding to the myosin VI structural (Insert 2) and regulatory (IQ) light chain sites are distinct from those of calmodulin and provide a basis for specialized myosin VI function. The androcam N lobe noncanonically binds a single Ca2þ and is locked in a “closed” conformation, causing androcam to contact the Insert 2 site with its C lobe only. Androcam replacing calmodulin at Insert 2 will increase myosin VI lever arm flexibility, which may favor the compact monomeric form of myosin VI that functions on the actin cones by facilitating the collapse of the C-terminal region onto the motor domain. The tethered androcam N lobe could stabilize the monomer through contacts with C-terminal portions of the motor or recruit other components to the actin cones. Androcam binds the IQ site at all calcium levels, constitutively mimicking a conformation adopted by calmodulin only at intermediate calcium levels. Thus, androcam replacing calmodulin at IQ will abolish a Ca2þ-regulated, calmodulin-mediated myosin VI structural change. We propose that the N lobe prevents androcam from interfering with other calmodulin- mediated Ca2þ signaling events. We discuss how gene duplication and mutations that selectively stabilize one of the many conformations available to calmodulin support the molecular evolution of structurally and functionally distinct calmodulin-like proteins.
dc.embargo.termsnone
dc.identifier.citationJoshi, Mehul K., Moran, Sean, Beckingham, Kathleen M., et al.. "Structure of androcam supports specialized interactions with myosin VI." <i>Proceedings of the National Academy of Sciences,</i> 109, no. 33 (2012) National Academy of Sciences: 13290-13295. http://dx.doi.org/10.1073/pnas.1209730109.
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1209730109
dc.identifier.urihttps://hdl.handle.net/1911/71757
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.subject.keywordchemical exchange
dc.subject.keywordchemical shift perturbation
dc.subject.keywordEF-hand
dc.subject.keywordNMR
dc.titleStructure of androcam supports specialized interactions with myosin VI
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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