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Structure paper

TitleVIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation.
Journal, issue, pagesScience, Vol. 393, Issue 6817, Page 1236-1240, Year 2026
Publish dateSep 17, 2026
AuthorsPeter H Yoon / Trevor A Docter / Zeyuan Terry Zhang / Kenneth Loi / Santiago C Lopez / Luis E Valentin-Alvarado / Owen T Tuck / Stephen G Brohawn / Jennifer A Doudna /
PubMed AbstractViral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN ...Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo-electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.
External linksScience / PubMed:42752121
MethodsEM (single particle)
Resolution2.5 - 3.5 Å
Structure data

77155

35se

EMDB-77155, PDB-35se:
VIPR Binary Complex - Consensus Conformation
Method: EM (single particle) / Resolution: 2.68 Å

77156

35sf

EMDB-77156, PDB-35sf:
VIPR Binary Complex with one filament
Method: EM (single particle) / Resolution: 2.85 Å

77157

35sg

EMDB-77157, PDB-35sg:
VIPR Binary Complex with two filaments
Method: EM (single particle) / Resolution: 2.7 Å

77176

35sy

EMDB-77176, PDB-35sy:
VIPR Ternary Complex with a pre-unwound dsDNA substrate, 11 subunits
Method: EM (single particle) / Resolution: 3.17 Å

77183

35tr

EMDB-77183, PDB-35tr:
VIPR Ternary Complex with a pre-unwound dsDNA substrate, 12 subunits
Method: EM (single particle) / Resolution: 3.13 Å

77184

35tw

EMDB-77184, PDB-35tw:
VIPR Ternary Complex with an ssRNA substrate, Closed Conformation
Method: EM (single particle) / Resolution: 2.94 Å

77185

35tx

EMDB-77185, PDB-35tx:
VIPR Ternary Complex with an ssRNA substrate, Closed Conformation, 11 subunits
Method: EM (single particle) / Resolution: 2.76 Å

77731

36pb

EMDB-77731, PDB-36pb:
VIPR Ternary Complex with an ssDNA substrate, 10 subunits
Method: EM (single particle) / Resolution: 3.1 Å

77732

36pc

EMDB-77732, PDB-36pc:
VIPR Ternary Complex with an ssDNA substrate, 11 subunits
Method: EM (single particle) / Resolution: 3.0 Å

77733

36pd

EMDB-77733, PDB-36pd:
P. fulva VIPR Ternary Complex with four subunits
Method: EM (single particle) / Resolution: 2.8 Å

77734

36pe

EMDB-77734, PDB-36pe:
VIPR Ternary Complex with an ssDNA substrate, 12 subunits
Method: EM (single particle) / Resolution: 3.0 Å

77735

36pf

EMDB-77735, PDB-36pf:
VIPR Ternary Complex with a duplex dsDNA substrate, 5 subunits
Method: EM (single particle) / Resolution: 3.4 Å

77736

36pg

EMDB-77736, PDB-36pg:
VIPR Ternary Complex with a duplex dsDNA substrate, 11 subunits
Method: EM (single particle) / Resolution: 3.5 Å

77738

36pj

EMDB-77738, PDB-36pj:
VIPR Ternary Complex with a duplex dsDNA substrate, 7 subunits
Method: EM (single particle) / Resolution: 3.2 Å

77739

36pk

EMDB-77739, PDB-36pk:
VIPR Ternary Complex with a duplex dsDNA substrate, 10 subunits
Method: EM (single particle) / Resolution: 3.3 Å

77740

36pm

EMDB-77740, PDB-36pm:
VIPR Ternary Complex with a duplex dsDNA substrate, 9 subunits
Method: EM (single particle) / Resolution: 3.2 Å

77742

36po

EMDB-77742, PDB-36po:
VIPR Ternary Complex with a duplex dsDNA substrate, 8 subunits
Method: EM (single particle) / Resolution: 3.2 Å

77745

36pr

EMDB-77745, PDB-36pr:
P. fulva VIPR Ternary Complex Consensus Conformation
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • suspvirus susp1
  • synthetic construct (others)
  • unidentified (others)
  • escherichia coli (E. coli)
  • pseudomonas fulva (bacteria)
KeywordsRNA BINDING PROTEIN/RNA / Ribonucleoprotein / VIPR / RNA Binding Protein / Binary Complex / RNA BINDING PROTEIN-RNA complex / RNA BINDING PROTEIN/RNA/DNA / Ternary Complex / RNA BINDING PROTEIN-RNA-DNA complex

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