6q5z

H-Vc7.2, H-superfamily conotoxin

spinqualitylabelsall models 6q5z Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q5z is a 1 chain structure with sequence from Conus victoriae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H72_CONVC Publication Abstract from PubMed Venomous marine cone snails produce peptide toxins (conotoxins) that bind ion channels and receptors with high specificity and therefore are important pharmacological tools. Conotoxins contain conserved cysteine residues that form disulfide bonds that stabilize their structures. To gain structural insight into the large, yet poorly characterized conotoxin H-superfamily, we used NMR and CD spectroscopy along with MS-based analyses to investigate H-Vc7.2 from Conus victoriae, a peptide with a VI/VII cysteine framework. This framework has Cys(I)-Cys(IV)/Cys(II)-Cys(V)/Cys(III)-Cys(VI) connectivities, which have invariably been associated with the inhibitor cystine knot (ICK) fold. However, the solution structure of recombinantly expressed and purified H-Vc7.2 revealed that although it displays the expected cysteine connectivities, H-Vc7.2 adopts a different fold consisting of two stacked beta-hairpins with opposing beta-strands connected by two parallel disulfide bonds, a structure homologous to the N-terminal region of the human granulin protein. Using structural comparisons, we subsequently identified several toxins and nontoxin proteins with this "mini-granulin" fold. These findings raise fundamental questions concerning sequence-structure relationships within peptides and proteins and the key determinants that specify a given fold. The three-dimensional structure of an H-superfamily conotoxin reveals a granulin fold arising from a common ICK cysteine framework.,Nielsen LD, Foged MM, Albert A, Bertelsen AB, Soltoft CL, Robinson SD, Petersen SV, Purcell AW, Olivera BM, Norton RS, Vasskog T, Safavi-Hemami H, Teilum K, Ellgaard L J Biol Chem. 2019 Apr 11. pii: RA119.007491. doi: 10.1074/jbc.RA119.007491. PMID:30975904 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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