Nature - USA (2020-10-15)

b

a

Mus

musculus

Rattus

norvegicus

Homo

sapiens

Nematostella vectensis

Crassostrea

gigas

Drosophila

melanogaster

Capnocytophaga

granulosa

Flavobacteriaceae sp. Bacteria

Vertebrates

Invertebrates

TMTIR

Danio rerio

Gallus gallus

Bombyx mori

Sus scrofa

Xenopus

laevis

Monosigabrevicollis

Bacterial STING–3',3'-cGAMP Oyster STING– 2 ',3'-cGAMP Anemone STING–2',3'-cGAMP Human STING–2',3'-cGAMP

N91

N172

G186(-CO)

G281 T303

G205(-CO) G166(-CO)

T263

D169

F92

E260

Y167

E300

Y206

E278

Y187

Side-chain interaction with phosphate

Aspartate direct interaction with guanosine

and phenylalanine base stacking

STING–CDN contacts

from base of binding pocke

t

STING–CDN contactswith nucleobase edge

STING–CDN contactsfrom β-strand “lid” region

R151

R153R153

R151

R250 R25 0

R256 R25 6

R272R 272

R27 (^8) R278 R238
R232 R232
R238
Arginine stacking between CDN bases
Lack of side-chain specific interaction with phosphate
Glutamate split interaction between guanosine and base stacked tyrosine
Arginine stacking between CDN bases and additional phosphodiester linkage-specific contacts
Sphingobacterium
faecium
Extended Data Fig. 10 | See next page for caption.