Аннотация
We describe here the first three-dimensional structure of the cardiac
L-type voltage-gated calcium channel (VGCC) purified from bovine
heart. The structure was determined by electron microscopy and single
particle analysis of negatively stained complexes, using the angular
reconstitution method. The cardiac VGCC can be isolated as a stable
dimer, as reported previously for the skeletal muscle VGCC, with
a central aqueous chamber formed by the two halves of the complex.
Moreover, we demonstrate that the dimeric cardiac VGCC binds the
dihydropyridine 3Hazidopine with a Kd approximately 310 pM. We
have compared the cardiac VGCC structure with the skeletal muscle
form, determined using the same reconstructive methodology, allowing
us to identify common and distinct features of the complexes. By
using antibody and lectin-gold labeling, we have localized the intracellular
beta polypeptides and the extracellular glycosylation sites of the
skeletal muscle VGCC, which can be correlated to the cardiac three-dimensional
structure. From the data presented here the assignment of the orientation
of the VGCC complexes with respect to the lipid bilayer is now possible.
A difference between the cardiac and skeletal muscle ion channels
is apparent in the putative transmembrane region, which would be
consistent with the absence of the gamma subunit in the cardiac VGCC
assembly.
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