6VM6

Structure of Acinetobacter baumannii Cap4 SAVED/CARF-domain containing receptor with the cyclic trinucleotide 2'3'3'-cAAA

Summary for 6VM6

• Entry DOI: 10.2210/pdb6vm6/pdb
• Descriptor: SAVED domain-containing protein, 2'-5'-Linked Cyclic RNA (5'-R(P*AP*AP*A)-3'), SULFATE ION, ... (4 entities in total)
• Functional Keywords: nuclease, duf4297, saved, carf, phage immunity, hydrolase
• Biological source: Acinetobacter sp. ATCC 27244; More
• Total number of polymer chains: 11
• Total formula weight: 318739.86

Authors

Lowey, B.,Whiteley, A.T.,Keszei, A.F.A.,Morehouse, B.R.,Antine, S.P.,Cabrera, V.,Schwede, F.,Mekalanos, J.J.,Shao, S.,Lee, A.S.Y.,Kranzusch, P.J. (deposition date: 2020-01-27, release date: 2020-06-17, Last modification date: 2024-03-06)

Primary citation

Lowey, B.,Whiteley, A.T.,Keszei, A.F.A.,Morehouse, B.R.,Mathews, I.T.,Antine, S.P.,Cabrera, V.J.,Kashin, D.,Niemann, P.,Jain, M.,Schwede, F.,Mekalanos, J.J.,Shao, S.,Lee, A.S.Y.,Kranzusch, P.J.
CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection.
Cell, 182:38-, 2020

PubMed Abstract: cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated protein 4 (Cap4) as a founding member of a diverse family of >2,000 bacterial receptors that respond to CD-NTase signals. Structures of Cap4 reveal a promiscuous DNA endonuclease domain activated through ligand-induced oligomerization. Oligonucleotide recognition occurs through an appended SAVED domain that is an unexpected fusion of two CRISPR-associated Rossman fold (CARF) subunits co-opted from type III CRISPR immunity. Like a lock and key, SAVED effectors exquisitely discriminate 2'-5'- and 3'-5'-linked bacterial cyclic oligonucleotide signals and enable specific recognition of at least 180 potential nucleotide second messenger species. Our results reveal SAVED CARF family proteins as major nucleotide second messenger receptors in CBASS and CRISPR immune defense and extend the importance of linkage specificity beyond mammalian cGAS-STING signaling.

PubMed: 32544385
DOI: 10.1016/j.cell.2020.05.019

Experimental method

X-RAY DIFFRACTION (2.1 Å)