Mutational studies have identified part of the S5-S6 loop of voltage-dependent K+ channels (P region) responsible for tetraethylammonium (TEA) block and permeation properties. Several scorpion peptide toxins — charybdotoxin (ChTX), kaliotoxin (KITX), and agitoxin (AgTX) — also block the channel with high affinity and specificity. Here, we examine the interaction predicted when the toxins are docked onto the molecular model of the K+ channel pore that we recently proposed. Docking with the model of the Kv1.3 channel started by location of Lys-27 side chain into the central axis of the pore, followed by energy minimization. In the optimal arrangement, Arg-24 of KITX or AgTX forms a hydrogen bond with the Asp-386 carboxyl of one subunit, and Asn-30 is in immediate contact with Asp-386 of the opposing subunit in the tetramer. Toxin residues in proximity to the side chain of Lys-27 (Phe-25, Thr-36, Met-29, and Ser-11 in KITX) interact with the four C-end His-404s. For ChTX the interaction with Asp-386 is reduced, but this is compensated by additional nonbonded interactions formed by Tyr-36 and Arg-34. Comparison of calculated energy of interaction of these specific toxin-channel residues with experimental studies reveals good agreement. The similar total calculated energy of interaction is consistent with the similar IC50 for Kv1.3 block by KITX and AgTX. Steric contacts of residues in position 380 of the S5-P linker with residues on the upper part of toxins permit reconstruction of the K+ channel outer vestibule walls, which are about 30 Å apart and about 9 Å high. Molecular modeling shows complementarity of the pore model to toxin spacial structures, and supports the proposal that the N-terminal borders of the P regions surround residues of their C-terminal halves.
The Journal of Membrane Biology – Springer Journals
Published: Aug 1, 1997
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera