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A common structural motif incorporating a cystine knot and a triple‐stranded β‐sheet in toxic and inhibitory polypeptides
Author(s) -
Pallaghy Paul K.,
Norton Raymond S.,
Nielsen Katherine J.,
Craik David J.
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560031022
Subject(s) - antiparallel (mathematics) , structural motif , stereochemistry , chemistry , beta sheet , cystine , biochemistry , protein structure , cysteine , enzyme , physics , quantum mechanics , magnetic field
Abstract A common structural motif consisting of a cystine knot and a small triple‐stranded β‐sheet has been defined from comparison of the 3‐dimensional structures of the polypeptides ω‐conotoxin GVIA ( Conus geographus ), kalata BI ( Oldenlandia affinis DC), and CMTI‐I ( Curcurbita maxima ). These 3 polypeptides have diverse biological activities and negligible amino acid sequence identity, but each contains 3 disulfide bonds that give rise to a cystine knot. This knot consists of a ring formed by the first 2 bonds (1–4 and 2–5) and the intervening polypeptide backbone, through which the third disulfide (3–6) passes. The other component of this motif is a triple‐stranded, anti‐parallel β‐sheet containing a minimum of 10 residues, XXC 2 , XC 5 X, XXC 6 X (where the numbers on the half‐cystine residues refer to their positions in the disulfide pattern). The presence in these polypeptides of both the cystine knot and antiparallel β‐sheet suggests that both structural features are required for the stability of the motif. This structural motif is also present in other protease inhibitors and a spider toxin. It appears to be one of the smallest stable globular domains found in proteins and is commonly used in toxins and inhibitors that act by blocking the function of larger protein receptors such as ion channels or proteases.