TABLE 5

μ- and μO-Conotoxins inhibiting Nav1.x sodium channels (μ-conotoxin loop formula CC1–8CC3–4C2–5C)

Cysteines are bolded and aligned separately for μ- and μO-conotoxins, with residues affecting sodium channel affinity underlined.

SpeciesNameDietSequence (Disulfide Bonded 1–4/2–5/3–6)Nav1.x SelectivityReference
123456
μ-Conotoxins
    C. bullatusBuIIIAPVTDRCC-K--GKRECGRW-CRDHSRC-C*2 ∼ 4 > 1 ∼ 3 > 6 > 5 > 7 ∼ 8Holford et al., 2009; Wilson et al., 2011a
BuIIIBPVGERCCKN--GKRGCGRW-CRDHSRC-C*4 > 2 > 3 > 1 > 6 > 5 > 7 ∼ 8Holford et al., 2009; Wilson et al., 2011a
BuIIICPIVDRCCNKGNGKRGCSRW-CRDHSRC-C*4 > ?Holford et al., 2009
    C. catusCIIIAP--GRCCE-GPN--GCSSRWCKDHARC-C*Amphibian skeletal/cardiac, TTX-RZhang et al., 2006b
    C. consorsCnIIIAP--GRCCDVPNA---CSGRWCRDHAQC-C*2 ∼ 4 > 6 ∼ 5 > 3 > 1 > 7 ∼ 8Zhang et al., 2006b; Wilson et al., 2011a
CnIIIBP--ZGCCGEPNL---CFTRWCRNNARC-CRQQAmphibian TTX-R (< 25%)Zhang et al., 2006b
    C. geographusGIIIAP--RDCCTOOKK---CKDRQCK-OQRC-CA*4 > 1 > 6 > 2 > 3 ∼ 5 ∼ 7 ∼ 8Cruz et al., 1985; Wilson et al., 2011a
GIIIBP--RDCCTOORK---CKDRRCK-OMKC-CA*4 > 2 > 3 > 5 > 7 > 8 > ?Cruz et al., 1985; Lewis et al., 2007
GIIICP--RDCCTOOKK---CKDRRCK-OLKC-CA*4 > 2 > N.D.Cruz et al., 1985
    C. kinoshitaiKIIIAP----CCN-------CSSKWCRDHSRC-C*2 > 4 > 6 > 1 ∼ 7 > 3 > 5 > 8Bulaj et al., 2005; Zhang et al., 2007; Wilson et al., 2011a
    C. magusMIIIAP--ZGCCNVPNG---CSGRWCRDHAQC-C*4 > 2 > 3 > 6 ∼ 1 > 5 > 7 ∼ 8Zhang et al., 2006b; Wilson et al., 2011a
    C. purpurascensPIIIAP-ZRLCCGFOKS---CRSRQCK-OHRC-C*4 > 6 ∼ 1 > 2 > 3 > 5 ∼ 7 ∼ 8Shon et al., 1998a; Wilson et al., 2011a
    C. pennaceusPnIVAM----CCKYGWT---C-LLGC-SP--CGCMolluscanFainzilber et al., 1995b
PnIVBM----CCKYGWT---C-WLGC-SP--CGCMolluscanFainzilber et al., 1995b
    C. striatusSIIIAP--ZNCCNGG-----CSSKWCRDHARC-C*2 > 4 > 6 > 1 ∼ 3 > 7 > 5 > 8Bulaj et al., 2005; Yao et al., 2008; Leipold et al., 2011; Wilson et al., 2011a
SIIIBP--ZNCCNGG-----CSSKWCKGHARC-C*4 > 2 > ?Schroeder et al., 2008
    C. stercusmuscarumSmIIIAP--ZRCCNGRRG---CSSRWCRDHSRC-C4 > 2 > 1 > 3 > 6 > 5 ∼ 7 > 8West et al., 2002; Wilson et al., 2011a
    C. striolatusSxIIIAP---RCCTGKKGS--CSGRACKN-LKC-CA*4 > 1 > 6 > 2 > 3 ∼ 5 ∼ 7 ∼ 8Walewska et al., 2008; Wilson et al., 2011a
SxIIIBP--ZKCCTGKKGS--CSGRACKN-LRC-CA*N.D.Walewska et al., 2008
    C. tulipaTIIIAP-RHGCCKGOKG---CSSRECR-OQHC-C*4 > 2 > 1 > 3 > 6 > 5 ∼ 7 ∼ 8Lewis et al., 2007; Wilson et al., 2011a
μO-Conotoxins
    C. litteratusLtVIIAVGECLGWSNYCTSHSICCSGECILSYCDIWN.D.Pi et al., 2007
LtVdV-DC------CPAKLLCCNPTTX-S > TTX-RLiu et al., 2007a
LtVICVWPCKVAGSPCGLVSECCGT-CNVLRNRCVN.D.Wang et al., 2008
    C. marmoreusMrVIAM-ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV8 > 7 > 4 > 2 > TTX-SFainzilber et al., 1995c; McIntosh et al., 1995; Safo et al., 2000; Daly et al., 2004; Zorn et al., 2006
MrVIBM-ACSKKWEYCIVPILGFVYCCPGLICGPFVCV8 > 4 > 2 ∼ 3 ∼ 5 ∼ 7 > 9Fainzilber et al., 1995b; Fainzilber et al., 1995c; McIntosh et al., 1995; Ekberg et al., 2006; Zorn et al., 2006
    C. geographusConotoxin-GSP-ACSGRGSRCOOQCCMGLRCGRGNPQKCIGAHγDV4 > 2 > N.D.Yanagawa et al., 1988; Hill et al., 1997
  • P, fish; M, molluscs; V, worms;

  • * , C-terminal amidation; N.D., not determined; TTX-S TTX-sensitive; TTX-R, TTX-resistant.