9JN9

Cryo-EM structure of human SLFN14

Summary for 9JN9

• Entry DOI: 10.2210/pdb9jn9/pdb
• EMDB information: 61620
• Descriptor: Protein SLFN14, ZINC ION (2 entities in total)
• Functional Keywords: dna/rna processing enzymes, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 209783.44

Authors

Luo, M.,Jia, X.D.,Wang, Z.W.,Yang, J.Y.,Zhang, Q.F.,Gao, S. (deposition date: 2024-09-23, release date: 2025-06-18, Last modification date: 2025-07-16)

Primary citation

Luo, M.,Jia, X.,Wang, Z.W.,Yang, J.Y.,Wang, W.,Chen, J.,Ou, J.Y.,Feng, J.X.,Yu, B.,Wang, S.,Huang, L.,Morgan, N.V.,Deng, K.,Chen, T.,Zhang, Q.,Gao, S.
Structural and functional characterization of human SLFN14.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: The Schlafen (SLFN) family of proteins are a group of DNA/RNA processing enzymes with emerging importance in human health and disease, where their functions are implicated in a variety of immunological and anti-tumor processes. Here, we present the cryo-electron microscopy structure of full-length human SLFN14, a member with antiviral activity and linked to an inherited bleeding disorder. SLFN14 is composed of an RNase domain, a SWADL domain, and a two-lobe helicase domain. SLFN14 exhibited strong RNase activity over different substrates, and the positively charged patches at the valley of the RNase domain, which contains the thrombocytopenia-related missense mutation sites, are crucial for binding oligonucleotides. SLFN14 lacks helicase activity, which can be attributed to the inability to bind ATP and the absence of positive charges at the canonical DNA-binding site of its RecA-like folds. SLFN14 is structurally similar to SLFN11, but differs from SLFN5 in the orientation of the helicase domain. Live-cell fluorescence resonance energy transfer (FRET) assays and AlphaFold2 analysis hinted that SLFN14 may adopt multiple conformations in cells. These results provide detailed structural and biochemical features of SLFN14, and greatly expand our knowledge of the functional diversity of the SLFN family.

PubMed: 40464691
DOI: 10.1093/nar/gkaf484

Experimental method

ELECTRON MICROSCOPY (3.36 Å)