Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices enhancing protein functionality
By R. Cooley, D. Arp, Paul Karplus. 2010
168 citations recorded by the source corpus.
Formally annotated π-helices are rare in protein structure but have been correlated with functional sites. Here, we analyze protein structures to show that π-helices are the same as structures known as α-bulges, α-aneurisms, π-bulges, and looping-outs and are evolutionarily derived by the insertion of a single residue into an α-helix. This newly discovered evolutionary origin explains both why π-helices are cryptic, being rarely annotated despite occurring in 15% of known proteins, and why they tend to be associated with function. An analysis of the π-helices in the diverse ferritin-like superfamily illustrates their tendency to be conserved in protein families, and identifies a putative π-helix-containing primordial precursor, a “missing link” intermediary form of the ribonucleotide reductase family, vestigial π-helices, and a novel function for π-helices we term peristaltic-like shifts. This new understanding of π-helices paves the way for this generally overlooked motif to become a noteworthy feature that will aid tracing the evolution of many protein families, guide investigations of protein and π-helix functionality, and contribute additional tools to the protein engineering toolkit.
Subfields: Molecular Biology
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In Molecular Biology
- Robbie P. Joosten
- G. Vriend
- Elmar Krieger
- Tim A. H. te Beek
- Anastassis Perrakis
- G. Murshudov
- Mikhail Markovsky
- Sari Sabban
Citations in the corpus
- BeStSel: webserver for secondary structure and fold prediction for protein CD spectroscopy (2022, unknown): “In the earlier version of DSSP, residues in (cid:4) -helices might have been erroneously assigned to (cid:2) -helix.”
- A series of PDB-related databanks for everyday needs (2014, methodology): “The determination of -helices still follows the original description by Kabsch and Sander (8), but the assignment of -helices is now given precedence over the assignment of -helices, which should prevent underestimating the number of -helices (9,10).”
- Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer (2020, background): “Furthermore, helix αAdisplays a substantial kink centered at about its midpoint that is hallmarked by a π-helical turn, a structural feature that has been linked to the enhancement of protein functionality (110).”