Peptide-RNA Coacervates as a Cradle for the Evolution of Folded Domains

Manas Seal, Orit Weil-Ktorza, Dragana Despotovic, Dan Tawfik, Koby Levy, Norman Metanis, Liam Longo, Daniella Goldfarb, Dragana Despotović, Yaakov Levy

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Peptide-RNA coacervates can result in the concentration and compartmentalization of simple biopolymers. Given their primordial relevance, peptide-RNA coacervates may have also been a key site of early protein evolution. However, the extent to which such coacervates might promote or suppress the exploration of novel peptide conformations is fundamentally unknown. To this end, we used electron paramagnetic resonance spectroscopy (EPR) to characterize the structure and dynamics of an ancient and ubiquitous nucleic acid binding element, the helix-hairpin-helix (HhH) motif, alone and in the presence of RNA, with which it forms coacervates. Double electron–electron resonance (DEER) spectroscopy applied to singly labeled peptides containing one HhH motif revealed the presence of dimers, even in the absence of RNA. Moreover, dimer formation is promoted upon RNA binding and was detectable within peptide-RNA coacervates. DEER measurements of spin-diluted, doubly labeled peptides in solution indicated transient α-helical character. The distance distributions between spin labels in the dimer and the signatures of α-helical folding are consistent with the symmetric (HhH)2-Fold, which is generated upon duplication and fusion of a single HhH motif and traditionally associated with dsDNA binding. These results support the hypothesis that coacervates are a unique testing ground for peptide oligomerization and that phase-separating peptides could have been a resource for the construction of complex protein structures via common evolutionary processes, such as duplication and fusion.
שפה מקוריתאנגלית
עמודים (מ-עד)14150-14160
מספר עמודים11
כתב עתJournal of the American Chemical Society
כרך144
מספר גיליון31
תאריך מקוון מוקדם29 יולי 2022
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 10 אוג׳ 2022

ASJC Scopus subject areas

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  • ???subjectarea.asjc.1300.1303???
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