8FMF

Structure of CBASS Cap5 from Pseudomonas syringae as an activated tetramer with the cyclic dinucleotide 3'2'-c-diAMP ligand (1 tetramer in the AU)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

Starting Model: in silico
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This is version 1.2 of the entry. See complete history


Literature

Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides.

Rechkoblit, O.Sciaky, D.Kreitler, D.F.Buku, A.Kottur, J.Aggarwal, A.K.

(2024) Nat Struct Mol Biol 31: 767-776

  • DOI: https://doi.org/10.1038/s41594-024-01220-x
  • Primary Citation of Related Structures:  
    8FM1, 8FMF, 8FMG, 8FMH

  • PubMed Abstract: 

    The bacterial cyclic oligonucleotide-based antiphage signaling system (CBASS) is similar to the cGAS-STING system in humans, containing an enzyme that synthesizes a cyclic nucleotide on viral infection and an effector that senses the second messenger for the antiviral response. Cap5, containing a SAVED domain coupled to an HNH DNA endonuclease domain, is the most abundant CBASS effector, yet the mechanism by which it becomes activated for cell killing remains unknown. We present here high-resolution structures of full-length Cap5 from Pseudomonas syringae (Ps) with second messengers. The key to PsCap5 activation is a dimer-to-tetramer transition, whereby the binding of second messenger to dimer triggers an open-to-closed transformation of the SAVED domains, furnishing a surface for assembly of the tetramer. This movement propagates to the HNH domains, juxtaposing and converting two HNH domains into states for DNA destruction. These results show how Cap5 effects bacterial cell suicide and we provide proof-in-principle data that the CBASS can be extrinsically activated to limit bacterial infections.


  • Organizational Affiliation

    Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SAVED domain-containing protein
A, B, C, D
388Pseudomonas syringaeMutation(s): 0 
UniProt
Find proteins for A0A2P0QGK5 (Pseudomonas syringae pv. actinidiae)
Explore A0A2P0QGK5 
Go to UniProtKB:  A0A2P0QGK5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A2P0QGK5
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Y4F (Subject of Investigation/LOI)
Query on Y4F

Download Ideal Coordinates CCD File 
E [auth A],
N [auth B],
R [auth C],
W [auth D]
Cyclic (adenosine-(2'-5')-monophosphate-adenosine-(3'-5')-monophosphate
C20 H24 N10 O12 P2
UZFVIESUDFOPOB-XPWFQUROSA-N
RWB
Query on RWB

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J [auth A]dodecaethylene glycol monomethyl ether
C25 H52 O13
PLQZJIIDLZRWBG-UHFFFAOYSA-N
P6G
Query on P6G

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S [auth C]HEXAETHYLENE GLYCOL
C12 H26 O7
IIRDTKBZINWQAW-UHFFFAOYSA-N
GOL
Query on GOL

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F [auth A]
G [auth A]
H [auth A]
I [auth A]
O [auth B]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
O [auth B],
X [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

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K [auth A],
P [auth B],
T [auth C],
Y [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

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AA [auth D]
L [auth A]
M [auth A]
Q [auth B]
U [auth C]
AA [auth D],
L [auth A],
M [auth A],
Q [auth B],
U [auth C],
V [auth C],
Z [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.536α = 90
b = 83.536β = 90
c = 401.96γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM13170

Revision History  (Full details and data files)

  • Version 1.0: 2024-02-07
    Type: Initial release
  • Version 1.1: 2024-02-21
    Changes: Database references
  • Version 1.2: 2024-05-29
    Changes: Database references