1s6x
From Proteopedia
|
Solution structure of VSTx
Overview
VSTx1 is a voltage sensor toxin from the spider Grammostola spatulata that, inhibits KvAP, an archeabacterial voltage-activated K(+) channel whose, X-ray structure has been reported. Although the receptor for VSTx1 and the, mechanism of inhibition are unknown, the sequence of the toxin is related, to hanatoxin (HaTx) and SGTx, two toxins that inhibit eukaryotic, voltage-activated K(+) channels by binding to voltage sensors. VSTx1 has, been recently shown to interact equally well with lipid membranes that, contain zwitterionic or acidic phospholipids, and it has been proposed, that the toxin receptor is located within a region of the channel that is, submerged in the membrane. As a first step toward understanding the, inhibitory mechanism of VSTx1, we determined the three-dimensional, solution structure of the toxin using NMR. Although the structure of VSTx1, is similar to HaTx and SGTx in terms of molecular fold and amphipathic, character, the detailed positions of hydrophobic and surrounding charged, residues in VSTx1 are very different than what is seen in the other, toxins. The amphipathic character of VSTx1, notably the close apposition, of basic and hydrophobic residues on one face of the toxin, raises the, possibility that the toxin interacts with interfacial regions of the, membrane. We reinvestigated the partitioning of VSTx1 into lipid membranes, and find that VSTx1 partitioning requires negatively charged, phospholipids. Intrinsic tryptophan fluorescence and acrylamide quenching, experiments suggest that tryptophan residues on the hydrophobic surface of, VSTx1 have a diminished exposure to water when the toxin interacts with, membranes. The present results suggest that if membrane partitioning is, involved in the mechanism by which VSTx1 inhibits voltage-activated K(+), channels, then binding of the toxin to the channel would likely occur at, the interface between the polar headgroups and the hydrophobic phase of, the membrane.
About this Structure
1S6X is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel., Jung HJ, Lee JY, Kim SH, Eu YJ, Shin SY, Milescu M, Swartz KJ, Kim JI, Biochemistry. 2005 Apr 26;44(16):6015-23. PMID:15835890
Page seeded by OCA on Wed Nov 21 02:09:36 2007
