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The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding.

ABSTRACT: Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-A crystal structure of the mouse PDE2A regulatory segment reported in this paper reveals that the GAF A domain functions as a dimerization locus. The GAF B domain shows a deeply buried cGMP displaying a new cGMP-binding motif and is the first atomic structure of a physiological cGMP receptor with bound cGMP. Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches.

SUBMITTER: Martinez SE 

PROVIDER: S-EPMC130621 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding.

Martinez Sergio E SE   Wu Albert Y AY   Glavas Natalie A NA   Tang Xiao-Bo XB   Turley Stewart S   Hol Wim G J WG   Beavo Joseph A JA  

Proceedings of the National Academy of Sciences of the United States of America 20020923 20

Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-A crystal structure of the mous  ...[more]

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