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Energetic selection of topology in ferredoxins.

ABSTRACT: Models of early protein evolution posit the existence of short peptides that bound metals and ions and served as transporters, membranes or catalysts. The Cys-X-X-Cys-X-X-Cys heptapeptide located within bacterial ferredoxins, enclosing an Fe?S? metal center, is an attractive candidate for such an early peptide. Ferredoxins are ancient proteins and the simple ?+? fold is found alone or as a domain in larger proteins throughout all three kingdoms of life. Previous analyses of the heptapeptide conformation in experimentally determined ferredoxin structures revealed a pervasive right-handed topology, despite the fact that the Fe?S? cluster is achiral. Conformational enumeration of a model CGGCGGC heptapeptide bound to a cubane iron-sulfur cluster indicates both left-handed and right-handed folds could exist and have comparable stabilities. However, only the natural ferredoxin topology provides a significant network of backbone-to-cluster hydrogen bonds that would stabilize the metal-peptide complex. The optimal peptide configuration (alternating ?(L),?(R)) is that of an ?-sheet, providing an additional mechanism where oligomerization could stabilize the peptide and facilitate iron-sulfur cluster binding.

SUBMITTER: Kim JD

PROVIDER: S-EPMC3320576 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Energetic selection of topology in ferredoxins.

Kim J Dongun JD Rodriguez-Granillo Agustina A Case David A DA Nanda Vikas V Falkowski Paul G PG

PLoS computational biology 20120405 4

Models of early protein evolution posit the existence of short peptides that bound metals and ions and served as transporters, membranes or catalysts. The Cys-X-X-Cys-X-X-Cys heptapeptide located within bacterial ferredoxins, enclosing an Fe₄S₄ metal center, is an attractive candidate for such an early peptide. Ferredoxins are ancient proteins and the simple α+β fold is found alone or as a domain in larger proteins throughout all three kingdoms of life. Previous analyses of the heptapeptide conf ...[more]

PMID: 22496635

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Energetic selection of topology in ferredoxins.

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Energetic selection of topology in ferredoxins.

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