2lkb
From Proteopedia
(Difference between revisions)
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<StructureSection load='2lkb' size='340' side='right' caption='[[2lkb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2lkb' size='340' side='right' caption='[[2lkb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2lkb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mesobuthus_eupeus Mesobuthus eupeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKB OCA]. <br> | + | <table><tr><td colspan='2'>[[2lkb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mesobuthus_eupeus Mesobuthus eupeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKB OCA]. <br> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | </td></tr><tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lkb RCSB], [http://www.ebi.ac.uk/pdbsum/2lkb PDBsum]</span>< | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lkb RCSB], [http://www.ebi.ac.uk/pdbsum/2lkb PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
We report molecular characterization of a new multigene family of alpha-scorpion toxins (named MeuNaTxalpha-1 to MeuNaTxalpha-13) from the scorpion Mesobuthus eupeus. Of them, five native toxins (MeuNaTxalpha-1 to -5) were purified to homogeneity from the venom and the solution structure of MeuNaTxalpha-5 was solved by nuclear magnetic resonance. A systematic functional evaluation of MeuNaTxalpha-1, -2, -4 and -5 was conducted by two-electrode voltage-clamp recordings on seven cloned mammalian VGSCs (Nav1.2 to Nav1.8) and the insect counterpart DmNav1 expressed in Xenopus oocytes. Results show that all these four peptides slow inactivation of DmNav1 and are inactive on Nav1.8 at micromolar concentrations. However, they exhibit differential specificity for the other six channel isoforms (Nav1.2 to Nav1.7), in which MeuNaTxalpha-4 shows no activity on these isoforms and thus represents the first Mesobuthus-derived insect-selective alpha-toxin identified so far with a half maximal effective concentration (EC50) of 130 nM on DmNav1 and a half maximal lethal concentration (LD50) of about 200 pmol-g on the insect Musca domestica; MeuNaTxalpha-2 only affects Nav1.4; MeuNaTxalpha-1 and MeuNaTxalpha-5 have a wider range of channel spectrum, the former active on Nav1.2, Nav1.3, Nav1.6, and Nav1.7, whereas the latter acting on Nav1.3-Nav1.7. Remarkably, MeuNaTxalpha-4 and MeuNaTxalpha-5 are two nearly identical peptides differing by only one point mutation at site 50 (A50V) but exhibit rather different channel subtype selectivity, highlighting a switch role of this site in altering the target specificity. By the maximum likelihood models of codon substitution, we detected nine positively selected sites (PSSs) that could be involved in functional diversification of Mesobuthus alpha-toxins. The PSSs include site 50 and other seven sites located in functional surfaces of alpha-toxins. This work represents the first thorough investigation of evolutionary diversification of alpha-toxins derived from a specific scorpion lineage from the perspectives of sequence, structure, function and evolution. | We report molecular characterization of a new multigene family of alpha-scorpion toxins (named MeuNaTxalpha-1 to MeuNaTxalpha-13) from the scorpion Mesobuthus eupeus. Of them, five native toxins (MeuNaTxalpha-1 to -5) were purified to homogeneity from the venom and the solution structure of MeuNaTxalpha-5 was solved by nuclear magnetic resonance. A systematic functional evaluation of MeuNaTxalpha-1, -2, -4 and -5 was conducted by two-electrode voltage-clamp recordings on seven cloned mammalian VGSCs (Nav1.2 to Nav1.8) and the insect counterpart DmNav1 expressed in Xenopus oocytes. Results show that all these four peptides slow inactivation of DmNav1 and are inactive on Nav1.8 at micromolar concentrations. However, they exhibit differential specificity for the other six channel isoforms (Nav1.2 to Nav1.7), in which MeuNaTxalpha-4 shows no activity on these isoforms and thus represents the first Mesobuthus-derived insect-selective alpha-toxin identified so far with a half maximal effective concentration (EC50) of 130 nM on DmNav1 and a half maximal lethal concentration (LD50) of about 200 pmol-g on the insect Musca domestica; MeuNaTxalpha-2 only affects Nav1.4; MeuNaTxalpha-1 and MeuNaTxalpha-5 have a wider range of channel spectrum, the former active on Nav1.2, Nav1.3, Nav1.6, and Nav1.7, whereas the latter acting on Nav1.3-Nav1.7. Remarkably, MeuNaTxalpha-4 and MeuNaTxalpha-5 are two nearly identical peptides differing by only one point mutation at site 50 (A50V) but exhibit rather different channel subtype selectivity, highlighting a switch role of this site in altering the target specificity. By the maximum likelihood models of codon substitution, we detected nine positively selected sites (PSSs) that could be involved in functional diversification of Mesobuthus alpha-toxins. The PSSs include site 50 and other seven sites located in functional surfaces of alpha-toxins. This work represents the first thorough investigation of evolutionary diversification of alpha-toxins derived from a specific scorpion lineage from the perspectives of sequence, structure, function and evolution. | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:03, 1 May 2014
Evolutionary diversification of Mesobuthus alpha-scorpion toxins affecting sodium channels
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