The cyclotide family of circular miniproteins: Nature's combinatorial peptide template

被引:124
作者
Craik, DJ [1 ]
Cemazar, M
Wang, CKL
Daly, NL
机构
[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia
[2] Univ Queensland, Australian Res Council Special Res Ctr Funct & Ap, Brisbane, Qld 4072, Australia
关键词
cyclic cystine knot; kalata B1; NMR structure determination; molecular scaffold; drug design;
D O I
10.1002/bip.20451
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cyclotides are a recently discovered family of miniproteins that contain a head-to-tail cyclized backbone and a knotted arrangement of disulfide bonds. They are approximately 30 amino acids in size and are present in high abundance in plants from the Violaceae, Rubiaceae, and Cucurbitaceae families, with individual plants containing a suite of up to 100 cyclotides. They have a diverse range of biological activities, including uterotonic, anti-HIV, antitumor, and antimicrobial activities, although their natural function is likely that of defending their host plants from pathogens and pests. This review focuses on the structural aspects of cyclotides, which may be thought of as a natural combinatorial peptide template in which a wide range of amino acids is displayed on a compact molecular core made up of the cyclic cystine knot structural motif. Cyclotides are exceptionally stable and are resistant to denaturation via thermal, chemical, or enzymatic treatments. The struclural features that contribute to their remarkable stability are described ill this review. (c) 2006 Wiley Periodicals, Inc.
引用
收藏
页码:250 / 266
页数:17
相关论文
共 76 条
[61]   A COMMON STRUCTURAL MOTIF INCORPORATING A CYSTINE KNOT AND A TRIPLE-STRANDED BETA-SHEET IN TOXIC AND INHIBITORY POLYPEPTIDES [J].
PALLAGHY, PK ;
NIELSEN, KJ ;
CRAIK, DJ ;
NORTON, RS .
PROTEIN SCIENCE, 1994, 3 (10) :1833-1839
[62]   Twists, knots, and rings in proteins - Structural definition of the cyclotide framework [J].
Rosengren, KJ ;
Daly, NL ;
Plan, MR ;
Waine, C ;
Craik, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (10) :8606-8616
[63]   ELUCIDATION OF THE PRIMARY AND 3-DIMENSIONAL STRUCTURE OF THE UTEROTONIC POLYPEPTIDE KALATA B1 [J].
SAETHER, O ;
CRAIK, DJ ;
CAMPBELL, ID ;
SLETTEN, K ;
JUUL, J ;
NORMAN, DG .
BIOCHEMISTRY, 1995, 34 (13) :4147-4158
[64]  
SANDBERG F, 1965, CAHIERS MABOKE PARIS, V2, P5
[65]  
Schopke T., 1993, SCI PHARM, V61, P145
[66]   θ-defensins:: Cyclic antimicrobial peptides produced by binary ligation of truncated α-defensins [J].
Selsted, ME .
CURRENT PROTEIN & PEPTIDE SCIENCE, 2004, 5 (05) :365-371
[67]   A continent of plant defense peptide diversity:: Cyclotides in Australian Hybanthus (Violaceae) [J].
Simonsen, SM ;
Sando, L ;
Ireland, DC ;
Colgrave, ML ;
Bharathi, R ;
Göransson, U ;
Craik, DJ .
PLANT CELL, 2005, 17 (11) :3176-3189
[68]   Capped acyclic permutants of the circular protein kalata B1 [J].
Simonsen, SM ;
Daly, NL ;
Craik, DJ .
FEBS LETTERS, 2004, 577 (03) :399-402
[69]   Refined structure and metal binding site of the kalata B1 peptide [J].
Skjeldal, L ;
Gran, L ;
Sletten, K ;
Volkman, BF .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 399 (02) :142-148
[70]   Cytotoxic cyclotides from Viola tricolor [J].
Svangård, E ;
Göransson, U ;
Hocaoglu, Z ;
Gullbo, J ;
Larsson, R ;
Claeson, P ;
Bohlin, L .
JOURNAL OF NATURAL PRODUCTS, 2004, 67 (02) :144-147