A Single-Site Mutation Tunes Fluorescence and Chromophorylation of an Orange Fluorescent Cyanobacteriochrome.


Journal

Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360

Informations de publication

Date de publication:
04 10 2023
Historique:
revised: 06 07 2023
received: 11 05 2023
pmc-release: 04 10 2024
medline: 11 10 2023
pubmed: 10 7 2023
entrez: 9 7 2023
Statut: ppublish

Résumé

Cyanobacteriochrome (CBCR) cGMP-specific phosphodiesterase, adenylyl cyclase, and FhlA (GAF) domains bind bilin cofactors to confer sensory wavelengths important for various cyanobacterial photosensory processes. Many isolated GAF domains autocatalytically bind bilins, including the third GAF domain of CBCR Slr1393 from Synechocystis sp. PCC6803, which binds phycoerythrobilin (PEB) to yield a bright orange fluorescent protein. Compared to green fluorescent proteins, the smaller size and lack of an oxygen requirement for fluorescence make Slr1393g3 a promising platform for new genetically encoded fluorescent tools. Slr1393g3, however, shows low PEB binding efficiency (chromophorylation) at ~3 % compared to total Slr1393g3 expressed in E. coli. Here we used site-directed mutagenesis and plasmid redesign methods to improve Slr1393g3-PEB binding and demonstrate its utility as a fluorescent marker in live cells. Mutation at a single site, Trp496, tuned the emission over ~30 nm, likely by shifting autoisomerization of PEB to phycourobilin (PUB). Plasmid modifications for tuning relative expression of Slr1393g3 and PEB synthesis enzymes also improved chromophorylation and moving from a dual to single plasmid system facilitated exploration of a range of mutants via site saturation mutagenesis and sequence truncation. Collectively, the PEB/PUB chromophorylation was raised up to a total of 23 % with combined sequence truncation and W496H mutation.

Identifiants

pubmed: 37423892
doi: 10.1002/cbic.202300358
pmc: PMC10653908
mid: NIHMS1936845
doi:

Substances chimiques

Adenylyl Cyclases EC 4.6.1.1
Bacterial Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202300358

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM138223
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023 Wiley-VCH GmbH.

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Auteurs

Makena K Janis (MK)

Department of Chemistry, University of Houston, 3585 Cullen Blvd, Houston, TX, 77204, USA.

Wenping Zou (W)

Department of Chemistry, University of Houston, 3585 Cullen Blvd, Houston, TX, 77204, USA.

Melissa L Zastrow (ML)

Department of Chemistry, University of Houston, 3585 Cullen Blvd, Houston, TX, 77204, USA.

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Classifications MeSH