Origin of a folded repeat protein from an intrinsically disordered ancestor.
Repetitive proteins are thought to have arisen through the amplification of subdomain-sized peptides. Many of these originated in a non-repetitive context as cofactors of RNA-based replication and catalysis, and required the RNA to assume their active conformation. In search of the origins of one of the most widespread repeat protein families, the tetratricopeptide repeat (TPR), we identified several potential homologs of its repeated helical hairpin in non-repetitive proteins, including the putatively ancient ribosomal protein S20 (RPS20), which only becomes structured in the context of the ribosome. We evaluated the ability of the RPS20 hairpin to form a TPR fold by amplification and obtained structures identical to natural TPRs for variants with 2-5 point mutations per repeat. The mutations were neutral in the parent organism, suggesting that they could have been sampled in the course of evolution. TPRs could thus have plausibly arisen by amplification from an ancestral helical hairpin.
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Hongbo
H
Zhu
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Edgardo
0000-0002-2413-8261
E
Sepulveda
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Marcus D
0000-0001-6937-5677
MD
Hartmann
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Manjunatha
0000-0001-6570-7857
M
Kogenaru
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Astrid
A
Ursinus
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Eva
E
Sulz
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Reinhard
R
Albrecht
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Murray
M
Coles
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Jörg
J
Martin
Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Andrei N
0000-0002-1959-4836
AN
Lupas
D019143:Evolution, Molecular; D017510:Protein Folding; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D000074436:Tetratricopeptide Repeat / Q000235:genetics*
D012269:Ribosomal Proteins; C029611:ribosomal protein S20
TPR; amplification; ancient peptides; computational biology; protein evolution; protein folding; ribosomal protein; systems biology