Evidence for the emergence of ß-trefoils by 'Peptide Budding' from an IgG-like ß-sandwich.
PLoS Comput Biol
; 18(2): e1009833, 2022 02.
Article
in English
| MEDLINE | ID: covidwho-1731576
ABSTRACT
As sequence and structure comparison algorithms gain sensitivity, the intrinsic interconnectedness of the protein universe has become increasingly apparent. Despite this general trend, ß-trefoils have emerged as an uncommon counterexample They are an isolated protein lineage for which few, if any, sequence or structure associations to other lineages have been identified. If ß-trefoils are, in fact, remote islands in sequence-structure space, it implies that the oligomerizing peptide that founded the ß-trefoil lineage itself arose de novo. To better understand ß-trefoil evolution, and to probe the limits of fragment sharing across the protein universe, we identified both 'ß-trefoil bridging themes' (evolutionarily-related sequence segments) and 'ß-trefoil-like motifs' (structure motifs with a hallmark feature of the ß-trefoil architecture) in multiple, ostensibly unrelated, protein lineages. The success of the present approach stems, in part, from considering ß-trefoil sequence segments or structure motifs rather than the ß-trefoil architecture as a whole, as has been done previously. The newly uncovered inter-lineage connections presented here suggest a novel hypothesis about the origins of the ß-trefoil fold itself-namely, that it is a derived fold formed by 'budding' from an Immunoglobulin-like ß-sandwich protein. These results demonstrate how the evolution of a folded domain from a peptide need not be a signature of antiquity and underpin an emerging truth few protein lineages escape nature's sewing table.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Lotus
Language:
English
Journal:
PLoS Comput Biol
Journal subject:
Biology
/
Medical Informatics
Year:
2022
Document Type:
Article
Affiliation country:
Journal.pcbi.1009833
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