The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

Laura F. Landweber,Aaron David Goldman,Joshua T. Beatty

doi:10.1007/s00239-015-9722-8

Laura F. Landweber, Aaron David Goldman

Open Access

https://doi.org/10.1007/s00239-015-9722-8

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Abstract

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10 % of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00239-015-9722-8) contains supplementary material, which is available to authorized users.

Highlights

The emergence of life on Earth and the subsequent evolution of the last universal comment ancestor (LUCA) together represent a long process that passed through several distinct stages
We show that triosephosphate isomerase (TIM) barrel enzymes corresponding to the most taxonomically broad superfamilies have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution
We find that ribonucleotide reductase activating protein is predicted by structural similarity to be a half TIM barrel (Fig. 5a) that most closely matches a component of the full TIM barrel protein, 4Fe–4S-pyruvate formate-lyase activating enzyme (Fig. 5b)

Summary

Introduction

The emergence of life on Earth and the subsequent evolution of the last universal comment ancestor (LUCA) together represent a long process that passed through several distinct stages. Life emerged from an unknown geochemical context in which large proto-biomolecules were likely generated from smaller precursors. This prebiotic scenario must have been capable of producing precursor biopolymers that gave rise to the earliest genetic systems. The majority of evidence suggests that an RNA world scenario followed, in which a simple genetic system consisted of RNA genes that encoded a ribozyme-based metabolism (Gilbert 1986). While this hypothesis describes a predecessor to the current genetic system based on RNA or a similar biomolecule, it is possible, and some argue more likely, that many important metabolic reactions were catalyzed by amino acids, peptides, ions, and geochemical catalysts (Fig. 1b).

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