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PMID: 11032796 Published · ppublish English Journal Article

Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor.

The EMBO journal ·Vol. 19 ·No. 20 ·2000-10-16 ·Pages 5288-99

Ho YS, Burden LM, Hurley JH

Abstract

GAF domains are ubiquitous motifs present in cyclic GMP (cGMP)-regulated cyclic nucleotide phosphodiesterases, certain adenylyl cyclases, the bacterial transcription factor FhlA, and hundreds of other signaling and sensory proteins from all three kingdoms of life. The crystal structure of the Saccharomyces cerevisiae YKG9 protein was determined at 1.9 A resolution. The structure revealed a fold that resembles the PAS domain, another ubiquitous signaling and sensory transducer. YKG9 does not bind cGMP, but the isolated first GAF domain of phosphodiesterase 5 binds with K:(d) = 650 nM. The cGMP binding site of the phosphodiesterase GAF domain was identified by homology modeling and site-directed mutagenesis, and consists of conserved Arg, Asn, Lys and Asp residues. The structural and binding studies taken together show that the cGMP binding GAF domains form a new class of cyclic nucleotide receptors distinct from the regulatory domains of cyclic nucleotide-regulated protein kinases and ion channels.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Bacterial Proteins/chemistry Binding Sites Carrier Proteins/chemistry,classification,genetics,metabolism Contractile Proteins Crystallography, X-Ray Cyclic GMP/metabolism Cyclic Nucleotide Phosphodiesterases, Type 5 Fungal Proteins/chemistry,genetics,metabolism Intracellular Signaling Peptides and Proteins Microfilament Proteins/chemistry Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Phosphoric Diester Hydrolases/chemistry Photoreceptors, Microbial Profilins Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Recombinant Proteins/chemistry,genetics,metabolism Saccharomyces cerevisiae/chemistry,genetics Saccharomyces cerevisiae Proteins Sequence Alignment Signal Transduction
Chemicals
Bacterial Proteins Carrier Proteins Contractile Proteins Fungal Proteins Intracellular Signaling Peptides and Proteins Microfilament Proteins Photoreceptors, Microbial Profilins Recombinant Proteins Saccharomyces cerevisiae Proteins YKL069W protein, S cerevisiae cyclic GMP-binding protein photoactive yellow protein, Bacteria Phosphoric Diester Hydrolases PDE5 protein, S cerevisiae Cyclic Nucleotide Phosphodiesterases, Type 5 Cyclic GMP
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ho Y S
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0580, USA.
Burden L M
Hurley J H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.20.5288
Published
2000-10-16
Pages
5288-99
Language
English
Region
England
NLM ID
8208664
PMCID
PMC314001
Subset
IM
Databases
PDB
1F5M, 1FL4
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1093/emboj/19.20.5288 PMC Full Text View journal details
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