Frozen in Time: The History of Proteins

Abstract

The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of ribosomal evolution, ribosomal protein (rProtein) segments reveal an atomic level history of protein folding. The data support a model in which aboriginal oligomers evolved into globular proteins in a hierarchical step-wise process. Complexity of assembly and folding of polypeptide increased incrementally in concert with expansion of rRNA. (i) Short random coil proto-peptides bound to rRNA, and (ii) lengthened over time and coalesced into β–β secondary elements. These secondary elements (iii) accreted and collapsed, primarily into β-domains. Domains (iv) accumulated and gained complex super-secondary structures composed of mixtures of α-helices and β-strands. Early protein evolution was guided and accelerated by interactions with rRNA. rRNA and proto-peptide provided mutual protection from chemical degradation and disassembly. rRNA stabilized polypeptide assemblies, which evolved in a stepwise process into globular domains, bypassing the immense space of random unproductive sequences. Coded proteins originated as oligomers and polymers created by the ribosome, on the ribosome and for the ribosome. Synthesis of increasingly longer products was iteratively coupled with lengthening and maturation of the ribosomal exit tunnel. Protein catalysis appears to be a late byproduct of selection for sophisticated and finely controlled assembly.

Class I and II aminoacyl‐tRNA synthetase tRNA groove discrimination created the first synthetase–tRNA cognate pairs and was therefore essential to the origin of genetic coding

“…Characteristics of the operational code are consistent with recent suggestions that protein structures evolved coordinately with the alphabet size and that the evolution of the genetic code also traces the discovery of protein folding rules (5). Correlations between secondary and tertiary structures of ribosomal proteins and the estimated order of rRNA additions provoked a similar hypothesis from an entirely different direction (29). Those authors postulated staged protein evolution, earlier stages marked initially by the absence of secondary structures, followed by the presence of β-, then α-structures, and then only after a prolonged development of secondary structures, by the emergence of tertiary structures.…”

Class I and II aminoacyl-tRNA synthetase tRNA groove discrimination created the first synthetase•tRNA cognate pairs and was therefore essential to the origin of genetic coding

“…Characteristics of the operational code are consistent with recent suggestions that protein structures evolved coordinately with the alphabet size and that the evolution of the genetic code also traces the discovery of protein folding rules (4). Correlations between secondary and tertiary structures of ribosomal proteins and the estimated order of rRNA additions provoked a similar hypothesis from an entirely different direction (28). Those authors postulated staged protein evolution, earlier stages marked initially by the absence of secondary structures, followed by the presence of β-, then α-structures, and then only after a prolonged development of secondary structures, by the emergence of tertiary structures.…”

Simple yet functional phosphate-loop proteins

“…Second, while binding and hydrolysis of phosphorylated nucleosides (NTPs) is the hallmark of modern P-loop NTPases, we have uniquely observed that the P-loop prototypes not only interact with NTPs, but also and foremost, avidly bind RNA and ssDNA. This raises the tantalizing possibility that early P-loop proteins emerged in a context of polynucleotide binding, and RNA in particular (57). Although some potential to hydrolyze NTP might be attributed to our P-loop prototypes, the far more efficient enzymatic NTPase functions we see today were likely acquired at a later stage when higher sequence and structural complexity evolved, including the acquisition of a magnesium-binding site and an activesite cavity.…”