At the junction of Fox and the RNA World?

April 25, 2010

An interesting abstract that came across my desk:

Chemistry. 2010 Mar 15. [Epub ahead of print]
Putative One-Pot Prebiotic Polypeptides with Ribonucleolytic Activity.
López-Alonso JP, Pardo-Cea MA, Gómez-Pinto I, Fernández I, Chakrabartty A, Pedroso E, González C, Laurents DV.
Instituto de Química Física “Rocasolano” C.S.I.C. Serrano 119, 28006, Madrid (Spain), Fax: (+34) 91-564-2431.
KIA7, a peptide with a highly restricted set of amino acids (Lys, Ile, Ala, Gly and Tyr), adopts a specifically folded structure. Some amino acids, including Lys, Ile, Ala, Gly and His, form under the same putative prebiotic conditions, whereas different conditions are needed for producing Tyr, Phe and Trp. Herein, we report the 3D structure and conformational stability of the peptide KIA7H, which is composed of only Lys, Ile, Ala, Gly and His. When the imidazole group is neutral, this 20-mer peptide adopts a four-helix bundle with a specifically packed hydrophobic core. Therefore, one-pot prebiotic proteins with well-defined structures might have arisen early in chemical evolution. The Trp variant, KIA7W, was also studied. It adopts a 3D structure similar to that of KIA7H and its previously studied Tyr and Phe variants, but is remarkably more stable. When tested for ribonucleolytic activity, KIA7H, KIA7W and even short, unstructured peptides rich in His and Lys, in combination with Mg(++), Mn(++) or Ni(++) (but not Cu(++), Zn(++) or EDTA) specifically cleave the single-stranded region in an RNA stem-loop. This suggests that prebiotic peptide-divalent cation complexes with ribonucleolytic activity might have co-inhabited the RNA world.

Why is this interesting?  Because it adds to the body of work that shows that rather limited and nondescript polypeptides with clear enzymatic properties can easily be formed.  A tantalizing possibility is raised by the RNA structural preference of the catalyst described – namely, its preference for single-stranded regions.  This property would provide a strong selective advantage for structured RNAs in a prebiotic world populated by these (and similar) polypeptides.

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