A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.

PLoS Computational Biology
Alexandr P KornevLynn F Ten Eyck

Abstract

Cyclic nucleotides (cAMP and cGMP) regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB) domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels) using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1) the phosphate binding cassette (PBC), which binds the cAMP ribose-phosphate, 2) the "hinge," a flexible helix, which contacts the PBC, 3) the beta(2,3) loop, which provides precise positioning of an invariant arginine from the PBC, and 4) a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif). The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the beta(2,3) loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP) represents a trans-regulated CNB domain family: it does not contain the N3A-motif, ...Continue Reading

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Citations

Sep 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alexandr P KornevLynn F Ten Eyck
Feb 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Changbong HyeonJosé N Onuchic
May 1, 2009·The Journal of Biological Chemistry·Rahul DasGiuseppe Melacini
Mar 4, 2010·The Journal of Biological Chemistry·In-Ja L ByeonAngela M Gronenborn
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nadine L WicksEdgar C Young
Sep 15, 2009·Journal of Molecular Biology·Simon H J BrownSusan S Taylor
Feb 13, 2009·British Journal of Pharmacology·Gillian BorlandStephen J Yarwood
Jan 30, 2013·Biological Reviews of the Cambridge Philosophical Society·Juana M Gancedo
Jun 1, 2010·Protein Science : a Publication of the Protein Society·Timothy J SjobergSusan S Taylor
Sep 18, 2014·Biophysical Journal·Srinath KrishnamurthyGanesh S Anand
Aug 16, 2015·Biophysical Journal·Srinath KrishnamurthyGanesh S Anand
Jun 7, 2011·International Journal of Mass Spectrometry·Jun H LeeDarren E Casteel
Jul 7, 2015·Nature Communications·Robert D MalmstromRommie E Amaro
Jun 23, 2015·Biophysics Reviews·Ping ZhangSusan S Taylor
Aug 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Madoka AkimotoGiuseppe Melacini
Jan 15, 2009·Structure·Alexandr P Kornev, Susan S Taylor
Mar 9, 2011·The Journal of Biological Chemistry·Galen E Flynn, William N Zagotta
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Susan S TaylorAlexandr P Kornev
Jul 10, 2012·Nature Structural & Molecular Biology·Ho Jun LeeTom Alber
Mar 27, 2012·The Journal of Biological Chemistry·Subhalaxmi NambiGanesh S Anand
Feb 7, 2020·IUBMB Life·Florian EnzlerEduard Stefan
Nov 28, 2012·PloS One·Rajeevan SelvaratnamGiuseppe Melacini
Feb 12, 2017·The Journal of Biological Chemistry·Maria Fe LanfrancoRodrigo A Maillard
Dec 20, 2019·Molecular & Cellular Proteomics : MCP·Dario HermidaGuillermo Montoya
Jun 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Majida El BakkouriRaymond Hui
Nov 23, 2019·Cells·Alveena AhmedGiuseppe Melacini
Aug 1, 2019·Proceedings of the National Academy of Sciences of the United States of America·Tsan-Wen LuSusan S Taylor
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Dario HermidaGuillermo Montoya
May 7, 2021·The Journal of Biological Chemistry·Susan S TaylorLynn F Ten Eyck
Feb 14, 2012·Biophysical Journal·Rajeevan SelvaratnamGiuseppe Melacini

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Methods Mentioned

BETA
NMR

Software Mentioned

DSSP
Linux
PyMOL

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