Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

The Two GAF Domains in Phosphodiesterase 2A Have Distinct Roles in Dimerization and in cGMP Binding

Sergio E. Martinez, Albert Y. Wu, Natalie A. Glavas, Xiao-Bo Tang, Stewart Turley, Wim G. J. Hol and Joseph A. Beavo
Proceedings of the National Academy of Sciences of the United States of America
Vol. 99, No. 20 (Oct. 1, 2002), pp. 13260-13265
Stable URL: http://www.jstor.org/stable/3073384
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
The Two GAF Domains in Phosphodiesterase 2A Have Distinct Roles in Dimerization and in cGMP Binding
Preview not available

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-Å 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.

Page Thumbnails

  • Thumbnail: Page 
[13260]
    [13260]
  • Thumbnail: Page 
13261
    13261
  • Thumbnail: Page 
13262
    13262
  • Thumbnail: Page 
13263
    13263
  • Thumbnail: Page 
13264
    13264
  • Thumbnail: Page 
13265
    13265