Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America.
PLoS Comput Biol. 2012;8(4):e1002463. doi: 10.1371/journal.pcbi.1002463. Epub 2012 Apr 5.
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.
早期蛋白质进化模型假设存在短肽，这些短肽可以结合金属和离子，并作为转运体、膜或催化剂。位于细菌铁氧还蛋白中的 Cys-X-X-Cys-X-X-Cys 七肽，包围着一个 Fe₄S₄ 金属中心，是这种早期肽的一个有吸引力的候选物。铁氧还蛋白是古老的蛋白质，简单的 α+β 折叠结构在所有三个生命领域的更大蛋白质中单独存在或作为一个结构域存在。对实验确定的铁氧还蛋白结构中七肽构象的先前分析表明，尽管 Fe₄S₄ 簇是非手性的，但存在普遍的右手拓扑结构。与立方烷铁硫簇结合的模型 CGGCGGC 七肽的构象枚举表明，既可以存在左手折叠，也可以存在右手折叠，并且它们具有相当的稳定性。然而，只有天然铁氧还蛋白拓扑结构提供了一个重要的骨架到簇氢键网络，这将稳定金属-肽复合物。最佳肽构象（交替的α(L),α(R))是α-折叠，这提供了一种额外的机制，其中寡聚化可以稳定肽并促进铁硫簇结合。
