MiaB

MiaB is a gene family encoding tRNA i6A37 methylthiotransferase MiaB, a radical S-adenosylmethionine (SAM) enzyme that modifies specific tRNAs. In many bacteria and archaea, MiaB catalyzes the insertion of a thiol group into the isopentenyladenosine at position 37 (i6A37) of tRNA, converting it to ms2i6A37. This modification is part of the tRNA modification pathway that helps optimize codon-anticodon interactions during translation.

Mechanism and cofactors

MiaB operates as a radical SAM enzyme, using SAM to generate a 5'-deoxyadenosyl radical and a cysteine-derived sulfur source to install a methylthio group at the 37 position of tRNA. The reaction requires a [4Fe-4S] cluster and often involves an auxiliary sulfur donor system, such as a cysteine desulfurase pathway, to supply sulfur for the thiolation. Many MiaB proteins contain additional iron-sulfur cluster–binding motifs (SPASM-type) and RNA-binding regions that support substrate recognition and catalysis. These features place MiaB within the broader radical SAM and sulfurtransferase families.

Structure and domain organization

Typical MiaB proteins feature an N-terminal region associated with metal-sulfur cluster binding, a central radical SAM domain containing the characteristic CxxxCxxC motif, a THUMP domain implicated in tRNA recognition, and, in many variants, a C-terminal SPASM-like region with cysteine-rich motifs for auxiliary cluster coordination. The domain architecture supports binding to tRNA substrates and coordinating multi-step chemistry.

Distribution and significance

MiaB homologs are widely distributed in prokaryotes and are also found in some eukaryotic organelles, reflecting the conserved importance of tRNA thiolation for accurate translation. Studied as a model radical SAM enzyme, MiaB provides insight into sulfur transfer chemistry, enzyme architecture, and RNA modification mechanisms. Disruption of miaB can affect growth and translational efficiency in certain organisms, highlighting its biological relevance.