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Novel miniproteins engineered by the transfer of active sites to small natural scaffolds
Author(s) -
Vita Claudio,
Vizzavona Jean,
Drakopoulou Eugenia,
ZinnJustin Sophie,
Gilquin Bernard,
Ménez André
Publication year - 1998
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1998)47:1<93::aid-bip10>3.0.co;2-h
Subject(s) - chemistry , natural (archaeology) , biochemical engineering , combinatorial chemistry , engineering , archaeology , history
Small multidisulfide‐containing proteins are attractive structural templates to produce a biologically active conformation that mimics the binding surface of natural large proteins. In particular, the structural motif that is evolutionary conserved in all scorpion toxins has a small size (30–40 amino acid residues), a great structural stability, and high permissiveness for sequence mutation. This motif is composed of a β‐sheet and an α‐helix bridged in the interior core by three disulfides. We have used this motif successfully to transfer within its β‐sheet new functional sites, including the curaremimetic loop of a snake neurotoxin and the CDR2‐like site of human CD4. Accumulated evidence indicated that the two miniproteins produced, the curaremimetic miniprotein and the CD4 mimetic , contain the α/β fold that is characteristic of the scaffold used and bind respectively to the acetylcholine receptor and to the envelope gp120 of HIV‐1. Furthermore, the latter was shown to prevent viral infection of lymphocytes. These examples illustrate that, by the transfer of active sites to small and stable natural scaffolds, it is possible to engineer miniproteins reproducing, in part, the function of much larger proteins. Such miniproteins may be of great utility as tools in structure‐function studies and as leads in drug design. © 1998 John Wiley & Sons, Inc. Biopoly 47: 93–100, 1998