Unknown

Dataset Information

0

Biogenesis of the pore architecture of a voltage-gated potassium channel.


ABSTRACT: The pore domain of voltage-gated potassium (Kv) channels consists of transmembrane helices S5 and S6, the turret, the pore helix, the selectivity filter, and the loop preceding S6, with a tertiary reentrant structure between S5 and S6. Using biogenic intermediates, mass tagging (pegylation), and a molecular tape measure, we explored the possibility that the first stages of pore formation occur prior to oligomerization of the transmembrane core. Pegylation of introduced cysteines shows that the pore helix, but not the turret, forms a compact secondary structure in the terminal 20 ? of the ribosomal tunnel. We assessed the tertiary fold of the pore loop in monomeric constructs by determining the relative accessibilities of select cysteines using the kinetics of pegylation. Turret residues are accessible at the extracellular surface. In contrast, pore helix residues are less accessible. All-atom molecular dynamics simulations of a single Kv monomer in a solvated lipid membrane indicate that secondary and tertiary folds are stable over 650 ns. These results are consistent with acquisition of a tertiary reentrant pore architecture at the monomer stage of Kv biogenesis and begin to define a plausible sequence of folding events in the formation of Kv channels.

SUBMITTER: Gajewski C 

PROVIDER: S-EPMC3044366 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Biogenesis of the pore architecture of a voltage-gated potassium channel.

Gajewski Christine C   Dagcan Alper A   Roux Benoit B   Deutsch Carol C  

Proceedings of the National Academy of Sciences of the United States of America 20110207 8


The pore domain of voltage-gated potassium (Kv) channels consists of transmembrane helices S5 and S6, the turret, the pore helix, the selectivity filter, and the loop preceding S6, with a tertiary reentrant structure between S5 and S6. Using biogenic intermediates, mass tagging (pegylation), and a molecular tape measure, we explored the possibility that the first stages of pore formation occur prior to oligomerization of the transmembrane core. Pegylation of introduced cysteines shows that the p  ...[more]

Similar Datasets

| S-EPMC3387523 | biostudies-literature
| S-EPMC2266581 | biostudies-literature
| S-EPMC1304659 | biostudies-literature
| S-EPMC3244940 | biostudies-literature
| S-EPMC2712980 | biostudies-literature
| S-EPMC3103376 | biostudies-literature
| S-EPMC3970532 | biostudies-literature
| S-EPMC2565492 | biostudies-literature
| S-EPMC3072105 | biostudies-literature
| S-EPMC4084761 | biostudies-literature