31FW

Human tRNA ligase complex

Summary for 31FW

• Entry DOI: 10.2210/pdb31fw/pdb
• EMDB information: 58360
• Descriptor: Ashwin, Protein FAM98B, RNA transcription, translation and transport factor protein, ... (6 entities in total)
• Functional Keywords: ligase, trna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 187771.88

Authors

Pfleiderer, M.M.,Jinek, M. (deposition date: 2026-06-02, release date: 2026-09-30)

Primary citation

Pfleiderer, M.M.,Kleinwachter, M.,Nievergelt, A.S.,Boneberg, F.M.,Kroupova, A.,Martinez, J.,Jinek, M.
Structural framework for the assembly of the human tRNA ligase complex.
Nat Commun, 17:-, 2026

PubMed Abstract: In human cells, a subset of tRNA-encoding genes contain introns. These are removed by a spliceosome-independent pathway in which the tRNA splicing endonuclease complex catalyzes intron excision. The resulting exons are subsequently ligated by the tRNA-ligase complex (tRNA-LC), comprising Ashwin, CGI-99, FAM98B, DDX1, and RTCB/HSPC117. The molecular architecture and functions of its non-catalytic subunits remain poorly understood. Using cryo-EM, we determined an atomic-resolution structure of human tRNA-LC. CGI-99, DDX1, and FAM98B form an α-helical bundle that contacts RTCB opposite its active site and anchors DDX1 via its C-terminal helix. FAM98B and CGI-99 form an extensively co-folded heterodimer that clamps Ashwin in a pincer-like structure. Structure-based mutagenesis supports the architecture of the complex. We further show that FAM98A and FAM98C assemble distinct RTCB-containing complexes lacking Ashwin, suggesting specialized cellular functions. Our results provide insights into the molecular assembly of the tRNA ligase complex, highlighting its functions in tRNA biogenesis and beyond.

PubMed: 42754576
DOI: 10.1038/s41467-026-77450-y

Experimental method

ELECTRON MICROSCOPY (3.3 Å)