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Although the chaperonin-mediated protein folding mechanism is well understood, the role of the conserved glycine and methionine-rich carboxy-terminal residues remains unclear. Bacteria with multiple chaperonins always retain at least one paralogue having the gly-met-rich C-terminus, indicating an essential conserved function. Here, we observed a stronger selection pressure on the paralogues with gly-met-rich C-termini, consistent with their ancestral functional importance. <jats:italic>E. coli<\/jats:italic> GroEL variants having mutations in their C-termini failed to functionally replace GroEL, suggesting the functional significance of the gly-met-rich C-termini. Further, our structural modelling and normal mode analysis showed that the C-terminal region shuttles between two cavity-specific conformations that correlate with the client-protein-binding apical domains, supporting C-termini\u2019s role in client protein encapsulation. Therefore, employing phylogenetic, genetic, and structural tools, we demonstrate that the gly-met-rich C-termini are functionally significant in chaperonin-mediated protein folding function. Owing to the pathogenic roles of the chaperonins having non-canonical C-termini, future investigations on the client protein selectivity will enable understanding the disease-specific client protein folding pathways and treatment options.<\/jats:p>","DOI":"10.1038\/s42003-025-07927-x","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T11:35:01Z","timestamp":1744112101000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic and structural insights into the functional importance of the conserved gly-met-rich C-terminal tails in bacterial chaperonins"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1370-2365","authenticated-orcid":false,"given":"C. M. 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