title: 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 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 conformation in experimentally determined ferredoxin structures revealed a pervasive right-handed topology, despite the fact that the Fe₄S₄ 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 α(L),α(R)) is that of an α-sheet, providing an additional mechanism where oligomerization could stabilize the peptide and facilitate iron-sulfur cluster binding.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: J Dongun
authors.initials: JD
authors.lastname: Kim
authors.forename: Agustina
authors.initials: A
authors.lastname: Rodriguez-Granillo
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.forename: Vikas
authors.initials: V
authors.lastname: Nanda
authors.forename: Paul G
authors.initials: PG
authors.lastname: Falkowski
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004735:Energy Transfer; D019143:Evolution, Molecular; D005288:Ferredoxins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D005288:Ferredoxins