Structure of androcam supports specialized interactions with myosin VI

Simple item page
dc.citation.firstpage13290en_US
dc.citation.issueNumber33en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.lastpage13295en_US
dc.citation.volumeNumber109en_US
dc.contributor.authorJoshi, Mehul K.en_US
dc.contributor.authorMoran, Seanen_US
dc.contributor.authorBeckingham, Kathleen M.en_US
dc.contributor.authorMacKenzie, Kevin R.en_US
dc.date.accessioned2013-08-22T21:53:25Zen_US
dc.date.available2013-08-22T21:53:25Zen_US
dc.date.issued2012en_US
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.en_US
dc.embargo.termsnoneen_US
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.en_US
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1209730109en_US
dc.identifier.urihttps://hdl.handle.net/1911/71757en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
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.en_US
dc.subject.keywordchemical exchangeen_US
dc.subject.keywordchemical shift perturbationen_US
dc.subject.keywordEF-handen_US
dc.subject.keywordNMRen_US
dc.titleStructure of androcam supports specialized interactions with myosin VIen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
PNAS-2012-Joshi-13290-5.pdf
Size:
1.77 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.61 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Biochemistry and Cell Biology Publications
Center for Research Computing
Faculty Publications