Details

Autor(en) / Beteiligte

• Kolodny, Rachel
• Nepomnyachiy, Sergey
• Tawfik, Dan S
• Ben-Tal, Nir
• Echave, Julian

Titel

Bridging Themes: Short Protein Segments Found in Different Architectures

Ist Teil von

• Molecular biology and evolution, 2021-05, Vol.38 (6), p.2191-2208

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract The vast majority of theoretically possible polypeptide chains do not fold, let alone confer function. Hence, protein evolution from preexisting building blocks has clear potential advantages over ab initio emergence from random sequences. In support of this view, sequence similarities between different proteins is generally indicative of common ancestry, and we collectively refer to such homologous sequences as “themes.” At the domain level, sequence homology is routinely detected. However, short themes which are segments, or fragments of intact domains, are particularly interesting because they may provide hints about the emergence of domains, as opposed to divergence of preexisting domains, or their mixing-and-matching to form multi-domain proteins. Here we identified 525 representative short themes, comprising 20–80 residues that are unexpectedly shared between domains considered to have emerged independently. Among these “bridging themes” are ones shared between the most ancient domains, for example, Rossmann, P-loop NTPase, TIM-barrel, flavodoxin, and ferredoxin-like. We elaborate on several particularly interesting cases, where the bridging themes mediate ligand binding. Ligand binding may have contributed to the stability and the plasticity of these building blocks, and to their ability to invade preexisting domains or serve as starting points for completely new domains.