Solution structure of the satiety factor, CART, reveals new functionality of a well-known fold.
Cocaine and amphetamine regulated transcript (CART) peptide has been shown to be an anorectic peptide that inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus. The C-terminal part containing the three disulfide bridges CART(48-89) is the biologically active part of the molecule affecting food intake. The solution structure of the active part of CART has a fold equivalent to other functionally distinct small proteins. CART consists mainly of turns and loops spanned by a compact framework composed by a few small stretches of antiparallel beta-sheet common to cystine knots.
Ludvigsen
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Novo Nordisk A/S, Novo Allé 1, DK-2880 Bagsvaerd, Denmark. svl@novonordisk.com
Thim
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Blom
A M
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Wulff
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BS
D000595:Amino Acid Sequence; D003553:Cystine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D004220:Disulfides; D009419:Nerve Tissue Proteins; D012996:Solutions; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D003553:Cystine