4l1d

Publication Abstract from PubMed

The vertebrate sodium (Nav) channel is composed of an ion-conducting alpha subunit and associated beta subunits. Here, we report the crystal structure of the human beta3 subunit immunoglobulin (Ig) domain, a functionally important component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the beta3 subunit Ig domain assembles as a trimer in the crystal asymmetric unit. Analytical ultracentrifugation confirmed the presence of Ig domain monomers, dimers, and trimers in free solution, and atomic force microscopy imaging also detected full-length beta3 subunit monomers, dimers, and trimers. Mutation of a cysteine residue critical for maintaining the trimer interface destabilized both dimers and trimers. Using fluorescence photoactivated localization microscopy, we detected full-length beta3 subunit trimers on the plasma membrane of transfected HEK293 cells. We further show that beta3 subunits can bind to more than one site on the Nav 1.5 alpha subunit and induce the formation of alpha subunit oligomers, including trimers. Our results suggest a new and unexpected role for the beta3 subunits in Nav channel cross-linking and provide new structural insights into some pathological Nav channel mutations.

Crystal Structure and Molecular Imaging of the Nav Channel beta3 Subunit Indicates a Trimeric Assembly.,Namadurai S, Balasuriya D, Rajappa R, Wiemhofer M, Stott K, Klingauf J, Edwardson JM, Chirgadze DY, Jackson AP J Biol Chem. 2014 Apr 11;289(15):10797-811. doi: 10.1074/jbc.M113.527994. Epub, 2014 Feb 24. PMID:24567321^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.