6XHH

Far-red absorbing dark state of JSC1_58120g3 with bound 18-1, 18-2 dihydrobiliverdin IXa (DHBV), the native chromophore precursor

Summary for 6XHH

• Entry DOI: 10.2210/pdb6xhh/pdb
• Descriptor: JSC1_58120g3, mesobiliverdin IX(alpha), 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: cyanobacteriochrome gaf domain phytochrome-superfamily 18-1, 18-2 dihydrobiliverdin, signaling protein
• Biological source: [Leptolyngbya] sp. JSC-1
• Total number of polymer chains: 2
• Total formula weight: 43723.19

Authors

Moreno, M.V.,Rockwell, N.C.,Fisher, A.J.,Lagarias, J.C. (deposition date: 2020-06-18, release date: 2020-10-28, Last modification date: 2024-10-30)

Primary citation

Moreno, M.V.,Rockwell, N.C.,Mora, M.,Fisher, A.J.,Lagarias, J.C.
A far-red cyanobacteriochrome lineage specific for verdins.
Proc.Natl.Acad.Sci.USA, 117:27962-27970, 2020

PubMed Abstract: Cyanobacteriochromes (CBCRs) are photoswitchable linear tetrapyrrole (bilin)-based light sensors in the phytochrome superfamily with a broad spectral range from the near UV through the far red (330 to 760 nm). The recent discovery of far-red absorbing CBCRs (frCBCRs) has garnered considerable interest from the optogenetic and imaging communities because of the deep penetrance of far-red light into mammalian tissue and the small size of the CBCR protein scaffold. The present studies were undertaken to determine the structural basis for far-red absorption by JSC1_58120g3, a frCBCR from the thermophilic cyanobacterium sp. JSC-1 that is a representative member of a phylogenetically distinct class. Unlike most CBCRs that bind phycocyanobilin (PCB), a phycobilin naturally occurring in cyanobacteria and only a few eukaryotic phototrophs, JSC1_58120g3's far-red absorption arises from incorporation of the PCB biosynthetic intermediate 18,18-dihydrobiliverdin (18,18-DHBV) rather than the more reduced and more abundant PCB. JSC1_58120g3 can also yield a far-red-absorbing adduct with the more widespread linear tetrapyrrole biliverdin IXα (BV), thus circumventing the need to coproduce or supplement optogenetic cell lines with PCB. Using high-resolution X-ray crystal structures of 18,18-DHBV and BV adducts of JSC1_58120g3 along with structure-guided mutagenesis, we have defined residues critical for its verdin-binding preference and far-red absorption. Far-red sensing and verdin incorporation make this frCBCR lineage an attractive template for developing robust optogenetic and imaging reagents for deep tissue applications.

PubMed: 33106421
DOI: 10.1073/pnas.2016047117

Experimental method

X-RAY DIFFRACTION (1.5 Å)