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Proc Natl Acad Sci U S A
2017 Nov 07;11445:E9520-E9528. doi: 10.1073/pnas.1708852114.
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Structural insights into binding of STAC proteins to voltage-gated calcium channels.
Wong King Yuen SM
,
Campiglio M
,
Tung CC
,
Flucher BE
,
Van Petegem F
.
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Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different CaV isoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II-III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of CaV1.2.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed
Adams,
Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs.
1990,
Pubmed
Avila,
Functional impact of the ryanodine receptor on the skeletal muscle L-type Ca(2+) channel.
2000,
Pubmed
Bannister,
Bridging the myoplasmic gap II: more recent advances in skeletal muscle excitation-contraction coupling.
2016,
Pubmed
Bannister,
Effects of inserting fluorescent proteins into the alpha1S II-III loop: insights into excitation-contraction coupling.
2009,
Pubmed
Barrett,
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.
2008,
Pubmed
Block,
Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle.
1988,
Pubmed
Bower,
Stac3 is required for myotube formation and myogenic differentiation in vertebrate skeletal muscle.
2012,
Pubmed
Campiglio,
STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads.
2017,
Pubmed
Dinkel,
ELM 2016--data update and new functionality of the eukaryotic linear motif resource.
2016,
Pubmed
Emsley,
Features and development of Coot.
2010,
Pubmed
Franzini-Armstrong,
Comparative ultrastructure of Ca2+ release units in skeletal and cardiac muscle.
1998,
Pubmed
Grabner,
Tagging with green fluorescent protein reveals a distinct subcellular distribution of L-type and non-L-type Ca2+ channels expressed in dysgenic myotubes.
1998,
Pubmed
Grabner,
The II-III loop of the skeletal muscle dihydropyridine receptor is responsible for the Bi-directional coupling with the ryanodine receptor.
1999,
Pubmed
Horstick,
Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy.
2013,
Pubmed
Kabsch,
XDS.
2010,
Pubmed
Kugler,
Structural requirements of the dihydropyridine receptor alpha1S II-III loop for skeletal-type excitation-contraction coupling.
2004,
Pubmed
Kurochkina,
SH3 domains: modules of protein-protein interactions.
2013,
Pubmed
Lau,
Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain.
2014,
Pubmed
Linsley,
Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3.
2017,
Pubmed
McCoy,
Phaser crystallographic software.
2007,
Pubmed
Murshudov,
REFMAC5 for the refinement of macromolecular crystal structures.
2011,
Pubmed
Nakai,
Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor.
1996,
Pubmed
Nakai,
Localization in the II-III loop of the dihydropyridine receptor of a sequence critical for excitation-contraction coupling.
1998,
Pubmed
Nelson,
Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.
2013,
Pubmed
Polster,
Stac3 has a direct role in skeletal muscle-type excitation-contraction coupling that is disrupted by a myopathy-causing mutation.
2016,
Pubmed
Polster,
Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca2+ channels.
2015,
Pubmed
Powell,
Formation of triads without the dihydropyridine receptor alpha subunits in cell lines from dysgenic skeletal muscle.
1996,
Pubmed
Reinholt,
Stac3 is a novel regulator of skeletal muscle development in mice.
2013,
Pubmed
Rios,
Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle.
,
Pubmed
Stamm,
Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia.
2008,
Pubmed
Takekura,
Restoration of junctional tetrads in dysgenic myotubes by dihydropyridine receptor cDNA.
1994,
Pubmed
Tanabe,
Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA.
1988,
Pubmed
Tanabe,
Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling.
1990,
Pubmed
Van Petegem,
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.
2004,
Pubmed
Van Petegem,
Ryanodine receptors: allosteric ion channel giants.
2015,
Pubmed
Wilkens,
Excitation-contraction coupling is unaffected by drastic alteration of the sequence surrounding residues L720-L764 of the alpha 1S II-III loop.
2001,
Pubmed
Zamponi,
The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.
2015,
Pubmed
