A mutually induced conformational fit underlies Ca2+-directed interactions between calmodulin and the proximal C terminus of KCNQ4 K+ channels.

The Journal of Biological Chemistry
Crystal R ArcherMark S Shapiro

Abstract

Calmodulin (CaM) conveys intracellular Ca2+ signals to KCNQ (Kv7, "M-type") K+ channels and many other ion channels. Whether this "calmodulation" involves a dramatic structural rearrangement or only slight perturbations of the CaM/KCNQ complex is as yet unclear. A consensus structural model of conformational shifts occurring between low nanomolar and physiologically high intracellular [Ca2+] is still under debate. Here, we used various techniques of biophysical chemical analyses to investigate the interactions between CaM and synthetic peptides corresponding to the A and B domains of the KCNQ4 subtype. We found that in the absence of CaM, the peptides are disordered, whereas Ca2+/CaM imposed helical structure on both KCNQ A and B domains. Isothermal titration calorimetry revealed that Ca2+/CaM has higher affinity for the B domain than for the A domain of KCNQ2-4 and much higher affinity for the B domain when prebound with the A domain. X-ray crystallography confirmed that these discrete peptides spontaneously form a complex with Ca2+/CaM, similar to previous reports of CaM binding KCNQ-AB domains that are linked together. Microscale thermophoresis and heteronuclear single-quantum coherence NMR spectroscopy indicated the C-lobe ...Continue Reading

References

Jan 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D J BeechB Hille
Jun 14, 1991·Cell·J R GeiserT N Davis
Mar 1, 1991·Journal of Neuroscience Methods·J RaeM Watsky
Jun 15, 1995·European Journal of Biochemistry·N TjandraA Bax
Jan 1, 1995·Annual Review of Biophysics and Biomolecular Structure·A Crivici, M Ikura
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Mar 17, 1999·Journal of Molecular Recognition : JMR·T NeufeldG Fleminger
Oct 8, 1999·Biochemistry·A MalmendalT Drakenberg
Nov 14, 2002·Journal of Agricultural and Food Chemistry·E Keowmaneechai, D J McClements
May 10, 2003·The Journal of Biological Chemistry·Quang-Kim TranAnthony Persechini
May 20, 2003·Nature Neuroscience·Naoto HoshiHaruhiro Higashida
Jun 18, 2003·The Journal of General Physiology·Nikita Gamper, Mark S Shapiro
Sep 23, 2003·The Journal of Physiology·James MaylieJohn P Adelman
May 20, 2005·Molecular Biology of the Cell·Nikita GamperMark S Shapiro
Nov 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mohammad ShahidullahIrwin B Levitan
May 12, 2006·Science's STKE : Signal Transduction Knowledge Environment·D Brent HallingSusan L Hamilton
Apr 7, 2007·The Journal of Physiology·Byung-Chang Suh, Bertil Hille
Jun 15, 2007·The Journal of Biological Chemistry·Tonghui XuEbenezer N Yamoah
Aug 21, 2007·Biophysical Journal·Yoshihisa KubotaM Neal Waxham
Nov 13, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ainhoa EtxeberriaAlvaro Villarroel
Dec 15, 2007·The Journal of General Physiology·Jessica M Rocheleau, William R Kobertz
Dec 18, 2007·Cell·David E Clapham
Jan 5, 2008·The Journal of Physiology·David PerozGildas Loussouarn
Jan 26, 2008·The Journal of Physiology·Yoni Haitin, Bernard Attali
Feb 2, 2008·The Journal of Physiology·Ciria C HernandezMark S Shapiro
May 6, 2008·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerLi-Wei Hung
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read

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Feb 23, 2020·International Journal of Molecular Sciences·Eider NúñezAlvaro Villarroel
May 23, 2021·BMC Biology·Janire UrrutiaAlvaro Villarroel
Sep 11, 2021·Frontiers in Molecular Biosciences·Jules NdeMargaret S Cheung

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