Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.
Voltage-dependent ion channels gate open in response to changes in cell membrane voltage. This form of gating permits the propagation of action potentials. We present two structures of the voltage-dependent K(+) channel KvAP, in complex with monoclonal Fv fragments (3.9 A) and without antibody fragments (8 A). We also studied KvAP with disulfide cross-bridges in lipid membranes. Analyzing these data in the context of the crystal structure of Kv1.2 and EPR data on KvAP we reach the following conclusions: (i) KvAP is similar in structure to Kv1.2 with a very modest difference in the orientation of its voltage sensor; (ii) mAb fragments are not the source of non-native conformations of KvAP in crystal structures; (iii) because KvAP contains separate loosely adherent domains, a lipid membrane is required to maintain their correct relative orientations, and (iv) the model of KvAP is consistent with the proposal of voltage sensing through the movement of an arginine-containing helix-turn-helix element at the protein-lipid interface.
Lee
Seok-Yong
SY
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Lee
Alice
A
Chen
Jiayun
J
MacKinnon
Roderick
R
D003460:Crystallization; D051663:Kv1.2 Potassium Channel / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D011487:Protein Conformation
D051663:Kv1.2 Potassium Channel; D008051:Lipid Bilayers; D008563:Membrane Lipids; D024642:Potassium Channels, Voltage-Gated