4L1D

Voltage-gated sodium channel beta3 subunit Ig domain

Summary for 4L1D

• Entry DOI: 10.2210/pdb4l1d/pdb
• Related: 1F97 1I8L 2X1X
• Descriptor: Sodium channel subunit beta-3 (2 entities in total)
• Functional Keywords: v-type immunoglobulin fold, sodium channel, voltage-gated, sodium channel alpha subunit, membrane, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: Q9NY72
• Total number of polymer chains: 3
• Total formula weight: 44498.11

Authors

Namadurai, S.,Weimhofer, M.,Rajappa, R.,Stott, K.,Klingauf, J.,Chirgadze, D.Y.,Jackson, A.P. (deposition date: 2013-06-03, release date: 2014-03-05, Last modification date: 2024-11-06)

Primary citation

Namadurai, S.,Balasuriya, D.,Rajappa, R.,Wiemhofer, M.,Stott, K.,Klingauf, J.,Edwardson, J.M.,Chirgadze, D.Y.,Jackson, A.P.
Crystal Structure and Molecular Imaging of the Nav Channel beta 3 Subunit Indicates a Trimeric Assembly.
J.Biol.Chem., 289:10797-10811, 2014

PubMed Abstract: The vertebrate sodium (Nav) channel is composed of an ion-conducting α subunit and associated β subunits. Here, we report the crystal structure of the human β3 subunit immunoglobulin (Ig) domain, a functionally important component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the β3 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 β3 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 β3 subunit trimers on the plasma membrane of transfected HEK293 cells. We further show that β3 subunits can bind to more than one site on the Nav 1.5 α subunit and induce the formation of α subunit oligomers, including trimers. Our results suggest a new and unexpected role for the β3 subunits in Nav channel cross-linking and provide new structural insights into some pathological Nav channel mutations.

PubMed: 24567321
DOI: 10.1074/jbc.M113.527994

Experimental method

X-RAY DIFFRACTION (2.5 Å)