1wt7: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="1wt7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wt7" /> '''Solution structure of BuTX-MTX: a butantoxin... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1wt7.gif|left|200px]]<br /><applet load="1wt7" size=" | [[Image:1wt7.gif|left|200px]]<br /><applet load="1wt7" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1wt7" /> | caption="1wt7" /> | ||
'''Solution structure of BuTX-MTX: a butantoxin-maurotoxin chimera'''<br /> | '''Solution structure of BuTX-MTX: a butantoxin-maurotoxin chimera'''<br /> | ||
==Overview== | ==Overview== | ||
Scorpion toxins interact with their target ion channels through multiple | Scorpion toxins interact with their target ion channels through multiple molecular contacts. Because a "gain of function" approach has never been described to evaluate the importance of the molecular contacts in defining toxin affinity, we experimentally examined whether increasing the molecular contacts between a toxin and an ion channel directly impacts toxin affinity. For this purpose, we focused on two scorpion peptides, the well-characterized maurotoxin with its variant Pi1-like disulfide bridging (MTX(Pi1)), used as a molecular template, and butantoxin (BuTX), used as an N-terminal domain provider. BuTX is found to be 60-fold less potent than MTX(Pi1) in blocking Kv1.2 (IC(50) values of 165 nM for BuTX versus 2.8 nM for MTX(Pi1)). Removal of its N-terminal domain (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6-fold, which is in agreement with docking simulation data showing the importance of this domain in BuTX-Kv1.2 interaction. Transfer of the BuTX N-terminal domain to MTX(Pi1) results in a chimera with five disulfide bridges (BuTX-MTX(Pi1)) that exhibits 22-fold greater affinity for Kv1.2 than MTX(Pi1) itself, in spite of the lower affinity of BuTX as compared to MTX(Pi1). Docking experiments performed with the 3-D structure of BuTX-MTX(Pi1) in solution, as solved by (1)H-NMR, reveal that the N-terminal domain of BuTX participates in the increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicate that acting on molecular contacts between a toxin and a channel is an efficient strategy to modulate toxin affinity. | ||
==About this Structure== | ==About this Structure== | ||
1WT7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | 1WT7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WT7 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Andreotti, N.]] | [[Category: Andreotti, N.]] | ||
[[Category: Ayeb, M | [[Category: Ayeb, M El.]] | ||
[[Category: Barek, S | [[Category: Barek, S M.]] | ||
[[Category: Chagot, B.]] | [[Category: Chagot, B.]] | ||
[[Category: Darbon, H.]] | [[Category: Darbon, H.]] | ||
| Line 21: | Line 21: | ||
[[Category: Mansuelle, P.]] | [[Category: Mansuelle, P.]] | ||
[[Category: Marrakchi, M.]] | [[Category: Marrakchi, M.]] | ||
[[Category: Sabatier, J | [[Category: Sabatier, J M.]] | ||
[[Category: Sampieri, F.]] | [[Category: Sampieri, F.]] | ||
[[Category: Visan, V.]] | [[Category: Visan, V.]] | ||
[[Category: Waard, M | [[Category: Waard, M De.]] | ||
[[Category: butantoxin]] | [[Category: butantoxin]] | ||
[[Category: k+ channels]] | [[Category: k+ channels]] | ||
| Line 32: | Line 32: | ||
[[Category: toxin affinity]] | [[Category: toxin affinity]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:47:51 2008'' | ||
