Discovery of a buried charge-network GFP-fold family spanning prokaryotes and eukaryotes (Draft manuscript)
The GFP fold has long been viewed as a specialized fluorescent scaffold found principally in marine animals. A structure-first search reveals a rare buried charge-network GFP-fold family spanning bacteria, fungi, and corals. Its members retain the eleven-stranded barrel and conserved chromophore-forming machinery but replace the canonical central tyrosine with methionine or other hydrophobic…
A recent study has unveiled a previously unknown family of GFP-fold proteins, spanning both prokaryotic and eukaryotic organisms. This discovery challenges the long-held belief that the green fluorescent protein (GFP) fold is solely present in marine animals. The research, conducted through a structure-first search, identified a rare buried charge-network GFP-fold family across a diverse array of life forms, including bacteria, fungi, and corals.
Members of this novel family maintain the characteristic eleven-stranded barrel structure and the machinery responsible for chromophore formation. However, they exhibit a unique modification: the central tyrosine residue, which is typically found in the canonical version of the GFP fold, is replaced by methionine or other hydrophobic residues. This alteration is believed to be an ancestral trait, predating the divergence of the family.
Unlike the conventional chromophore present in the GFP fold, the new family encloses an invariant five-residue network composed of two arginines, two glutamates, and Tyr168. This network, while less conserved than the protein surface, remains strongly conserved across evolutionary lineages. It occupies the most constrained sites in the protein structure and remains intact even under rigorous structure predictions and molecular dynamics simulations.
Interestingly, a fold-independent search identified the same two-cation/two-anion/tyrosine network in 238 members of the DUF2490 family, a separate outer-membrane beta-barrel family with no apparent connection to the GFP fold. This convergence suggests that the buried network is a result of convergent evolution, rather than a shared evolutionary origin.
Despite these intriguing findings, the biochemical function of this buried network remains a mystery. The study provides valuable insights into the broader sequence and chemical diversity of the GFP barrel, opening up new avenues for research into the potential roles of this unusual structural feature in various organisms.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
