Structure of the KvAP Voltage-Dependent K+ Channel and Its Dependence on the Lipid Membrane

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (43), p.15441-15446
• Main Authors: Lee, Seok-Yong, Lee, Alice, Chen, Jiayun, MacKinnon, Roderick
• Format: Article
• Language: English
• Subjects: Amino acids; Biological Sciences; Biophysics; CELL MEMBRANES; CRYSTAL STRUCTURE; Crystallization; Crystals; DISULFIDES; Electric potential; Immunoglobulin fragments; Ion channels; Ions; Kv1.2 Potassium Channel - chemistry; Lipid Bilayers - chemistry; LIPIDS; MATERIALS SCIENCE; Membrane Lipids - chemistry; Membrane proteins; MEMBRANES; national synchrotron light source; ORIENTATION; Potassium Channels, Voltage-Gated - chemistry; Protein Conformation; Proteins; Sensors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0507651102

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 ($3.9 \ring{A}$) and without antibody fragments ($8 \ring{A}$). 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.