Related Experiment Video
Updated: Jun 17, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights
Clemens C Heikaus1, Jayvardhan Pandit2, Rachel E Klevit1
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
None:
GAF domains regulate the catalytic activity of certain vertebrate cyclic nucleotide phosphodiesterases (PDEs) by allosteric, noncatalytic binding of cyclic nucleotides. GAF domains arranged in tandem are found in PDE2, -5, -6, -10, and -11, all of which regulate the cellular concentrations of the second messengers cAMP and/or cGMP. Nucleotide binding to GAF domains affects the overall conformation and the catalytic activity of full-length PDEs. The cyclic nucleotide-bound GAF domains from PDE2, -5, -6, and -10 all adopt a conserved fold but show subtle differences within the binding pocket architecture that account for a large range of nucleotide affinities and selectivity. NMR data and details from the structure of full-length nucleotide-free PDE2A reveal the dynamic nature and magnitude of the conformational change that accompanies nucleotide binding. The discussed GAF domain structures further reveal differences in dimerization properties and highlight the structural diversity within GAF domain-containing PDEs.
More Related Videos
Related Concept Videos
GTPases and their Regulation
Large G-proteins, also known...
GTPases and their Regulation
Large G-proteins, also known...
Activation and Inactivation of G Proteins
Phosphodiester Linkages
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
GPCRs Regulate Adenylyl Cylase Activity
Two...

