Cradle-loop barrels and the concept of metafolds in protein classification by natural descent

Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Spemannstr. 35, D-72076 Tübingen, Germany.
Current Opinion in Structural Biology (Impact Factor: 7.2). 07/2008; 18(3):358-65. DOI: 10.1016/
Source: PubMed


Current classification systems for protein structure show many inconsistencies both within and between systems. The metafold concept was introduced to identify fold similarities by consensus and thus provide a more unified view of fold space. Using cradle-loop barrels as an example, we propose to use the metafold as the next hierarchical level above the fold, encompassing a group of topologically related folds for which a homologous relationship has been substantiated. We see this as an important step on the way to a classification of proteins by natural descent.

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Available from: Andrei Lupas, Aug 30, 2014
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    • "Even remote homologs often still adopt the same fold, however in some instances homology could be established for proteins of different folds. These homologies were either established by the detection of homologous fold change [1]–[4] or by evidence for shared conserved supersecondary structures [4]–[8]. The latter are assumed to be remnants of an ancient peptide-RNA world [9]–[13]. "
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    PLoS ONE 10/2013; 8(10):e77074. DOI:10.1371/journal.pone.0077074 · 3.23 Impact Factor
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    • "Author's personal copy Table 2 The Drosophila Tight-binding Inhibitors. MEROPS Family Gene name FlyBase identifier AAs Domains Biological function/comment mRNA regulation Reference I1 Kazal CG31704 68 S þ I.C [28] CG14933 77 S CG42486 77 S CG17278 80 S Wnt receptor signalling þ I.C [30,78] Kaz1-B CG1220 97 S Sfp33A3 CG42474 99 S Seminal fluid protein Kaz1-A CG33790 103 S CG7695 145 S E(spl)m1 CG8342 165 S CG7906 354 C (2x) Ecdysone induced [30] CG7924 321 C (2x) Ecdysone Induced CG12716 418 S CG7173 564 C CG31758 605 Cx Cyclic nucleotide magu CG2264 613 Cx Longevity [46] CG13830 629 Cx CG32354 662 C (5x) Oatp58a CG30277 684 Cx Org. anion transport Oatp26F CG11332 692 Cx Org. "
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    • "structures (Alva et al., 2008). A subset of the representative domains from our v2003 CDD was used to conduct benchmark simulations of molecular dynamics (MD) force fields (Rueda et al., 2007). "
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