Reconstructing the Remote Origins of a Fold Singleton from a Flavodoxin-Like Ancestor

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Toledo-Patiño, Saacnicteh ; Chaubey, Manish ; Coles, Murray ; Höcker, Birte:
Reconstructing the Remote Origins of a Fold Singleton from a Flavodoxin-Like Ancestor.
In: Biochemistry. Bd. 58 (2019) Heft 48 . - S. 4790-4793.
ISSN 1520-4995
DOI: https://doi.org/10.1021/acs.biochem.9b00900

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Abstract

Evolutionary processes that led to the emergence of structured protein domains left footprints in the sequences of modern proteins. We searched for such hints employing state-of-the-art sequence analysis and found evidence that the HemD-like fold emerged from the flavodoxin-like fold through segment swap and gene duplication. To verify this hypothesis, we reverted these evolutionary steps experimentally, constructing a HemD-half that resulted in a protein with the canonical flavodoxin-like architecture. These results of fold reconstruction from the sequence of a different fold strongly support our hypothesis of common ancestry. It further illustrates the plasticity of modern proteins to form new folded proteins.