PMID: 7546741Sep 1, 1995Paper

Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels

Neuron
M D VarnumW N Zagotta

Abstract

Cyclic nucleotide-gated ion channels of retinal photoreceptors and olfactory neurons are differentially activated by ligands that vary only in their purine ring structure. The nucleotide selectivity of the bovine rod cyclic nucleotide-gated channel (cGMP > cIMP > cAMP) was significantly altered by neutralization of a single aspartic acid residue in the binding domain (cGMP > or = cAMP > cIMP). Substitution by a nonpolar residue at this position inverted agonist selectivity (cAMP > cIMP > or = cGMP). These effects resulted from an alteration in the relative ability of the agonists to promote the allosteric conformational change associated with channel activation, not from a modification in their initial binding affinity. We propose a general mechanism for guanine nucleotide discrimination, in common with that observed in high affinity GTP-binding proteins, involving the formation of a pair of hydrogen bonds between the aspartic acid side chain and N1 and N2 of the guanine ring.

References

Nov 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·G Lancelot, C Hélène
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·W AltenhofenU B Kaupp
Jan 1, 1986·Annual Review of Neuroscience·D Lancet
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J W KarpenD A Baylor
Jan 1, 1989·Annual Review of Neuroscience·K W Yau, D A Baylor
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·W N ZagottaR W Aldrich
Aug 1, 1988·Biophysical Journal·A L ZimmermanD A Baylor
Feb 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·I S SigalE M Scolnick
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·J BradleyK Zinn
Jan 1, 1994·Annual Review of Biophysics and Biomolecular Structure·F ZufallG M Shepherd
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·T Y ChenR S Molday
Nov 24, 1994·Nature·E H GouldingS A Siegelbaum
May 1, 1965·Journal of Molecular Biology·J MONODJ P CHANGEUX

❮ Previous
Next ❯

Citations

Jun 1, 1996·Journal of Bioenergetics and Biomembranes·W N Zagotta
Jan 1, 1995·Journal of Molecular Neuroscience : MN·C J Barnstable, Wei J-Y
May 20, 1998·Journal of Molecular Neuroscience : MN·J Y WeiC J Barnstable
Jun 21, 2005·Pharmacology & Therapeutics·Mirko BaruscottiDario Difrancesco
Nov 30, 2002·Trends in Pharmacological Sciences·Daniela Boassa, Andrea J Yool
Aug 1, 1996·Current Opinion in Neurobiology·R S Molday
Nov 1, 1996·Trends in Cardiovascular Medicine·M BielF Hofmann
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·S E JordtD Julius
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Neali ArmstrongEric Gouaux
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·C L TuckerJ B Hurley
Jan 13, 2011·The Journal of Biological Chemistry·Carmen A Ufret-VincentySharona E Gordon
Mar 1, 1997·The Journal of General Physiology·C Y Tang, D M Papazian
Aug 1, 1997·The Journal of General Physiology·S ShyngC G Nichols
Jan 5, 1999·The Journal of General Physiology·P PaolettiS A Siegelbaum
May 6, 1999·The Journal of General Physiology·E R Sunderman, W N Zagotta
May 6, 1999·The Journal of General Physiology·E R Sunderman, W N Zagotta
Jun 1, 2000·The Journal of General Physiology·D Guo, Z Lu
Aug 5, 2000·The Journal of General Physiology·S E Gordon
Aug 5, 2000·The Journal of General Physiology·T R MiddendorfD A Baylor
Aug 5, 2000·The Journal of General Physiology·T R Middendorf, R W Aldrich
Aug 1, 2002·The Journal of General Physiology·Lin BaoDaniel H Cox
Sep 1, 2004·The Journal of General Physiology·Crina M NimigeanChristopher Miller
Dec 2, 2004·The Journal of General Physiology·Kimberley B Craven, William N Zagotta
Aug 31, 2006·The Journal of General Physiology·Leon D Islas, William N Zagotta
Jun 1, 2011·The Journal of General Physiology·Wai-Fung WongEdgar C Young
Mar 27, 2013·The Journal of General Physiology·Gucan DaiMichael D Varnum
Mar 7, 2007·Chemical Senses·Kristina J WatsonTimothy A Gilbertson
Jun 17, 1998·The EMBO Journal·S J TuckerF M Ashcroft
May 6, 2009·Clinical and Experimental Pharmacology & Physiology·H Y KwanF P Leung
Jul 22, 1999·Annals of the New York Academy of Sciences·M C Broillet, S Firestein
Jul 22, 1999·Annals of the New York Academy of Sciences·B Santoro, G R Tibbs
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Kimberly Matulef, William N Zagotta
Feb 22, 2001·Annual Review of Physiology·U B Kaupp, R Seifert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.