Coupled tertiary folding and oligomerization of the T1 domain of Kv channels.
Acquisition of secondary, tertiary, and quaternary structure is critical to the fabrication, assembly, and function of ion channels, yet the relationship between these biogenic events remains unclear. We now address this issue in voltage-gated K(+) channels (Kv) for the T1 domain, an N-terminal Kv recognition domain that is responsible for subfamily-specific, efficient assembly of Kv subunits. This domain forms a 4-fold symmetric tetramer. We have identified residues along the axial T1-T1 interface that are critical for tertiary and quaternary structure, shown that mutations at one end of the axial T1 interface can perturb the crosslinking of an intersubunit cysteine pair at the other end, and demonstrated that tertiary folding and tetramerization of this Kv domain are coupled. A threshold level of tertiary folding is required for monomers to oligomerize. Coupling between tertiary and quaternary structure formation may be a common feature in the biogenesis of multimeric proteins.
Robinson
John M
JM
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Deutsch
Carol
C
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D003545:Cysteine / Q000737:chemistry; D004285:Dogs; D005260:Female; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000502:physiology; D014982:Xenopus laevis
D024642:Potassium Channels, Voltage-Gated; D003545:Cysteine