Intrinsically disordered C-terminal segments of voltage-activated potassium channels: a possible fishing rod-like mechanism for channel binding to scaffold proteins.
Membrane-embedded voltage-activated potassium channels (Kv) bind intracellular scaffold proteins, such as the Post Synaptic Density 95 (PSD-95) protein, using a conserved PDZ-binding motif located at the channels' C-terminal tip. This interaction underlies Kv-channel clustering, and is important for the proper assembly and functioning of the synapse. Here we demonstrate that the C-terminal segments of Kv channels adjacent to the PDZ-binding motif are intrinsically disordered. Phylogenetic analysis of the Kv channel family reveals a cluster of channel sequences belonging to three out of the four main channel families, for which an association is demonstrated between the presence of the consensus terminal PDZ-binding motif and the intrinsically disordered nature of the immediately adjacent C-terminal segment. Our observations, combined with a structural analogy to the N-terminal intra-molecular ball-and-chain mechanism for Kv channel inactivation, suggest that the C-terminal disordered segments of these channel families encode an inter-molecular fishing rod-like mechanism for K(+) channel binding to scaffold proteins.
Magidovich
Elhanan
E
Department of Life Sciences and the Zlotowski Center for Neurosciences, Ben Gurion University of the Negev Beer Sheva, Israel.
Fleishman
Sarel J
SJ
Yifrach
Ofer
O
D020816:Amino Acid Motifs; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D010802:Phylogeny; D015221:Potassium Channels / Q000737:chemistry*; D011485:Protein Binding; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry*
C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels