Regulatory and structural EF-hand motifs of neuronal calcium sensor-1: Mg 2+ modulates Ca 2+ binding, Ca 2+ -induced conformational changes, and equilibrium unfolding transitions

Journal of Molecular Biology
Penmatsa AravindYogendra Sharma

Abstract

Neuronal calcium sensor-1 (NCS-1) is a major modulator of Ca(2+) signaling with a known role in neurotransmitter release. NCS-1 has one cryptic (EF1) and three functional (EF2, EF3, and EF4) EF-hand motifs. However, it is not known which are the regulatory (Ca(2+)-specific) and structural (Ca(2+)- or Mg(2+)-binding) EF-hand motifs. To understand the specialized functions of NCS-1, identification of the ionic discrimination of the EF-hand sites is important. In this work, we determined the specificity of Ca(2+) binding using NMR and EF-hand mutants. Ca(2+) titration, as monitored by [(15)N,(1)H] heteronuclear single quantum coherence, suggests that Ca(2+) binds to the EF2 and EF3 almost simultaneously, followed by EF4. Our NMR data suggest that Mg(2+) binds to EF2 and EF3, thereby classifying them as structural sites, whereas EF4 is a Ca(2+)-specific or regulatory site. This was further corroborated using an EF2/EF3-disabled mutant, which binds only Ca(2+) and not Mg(2+). Ca(2+) binding induces conformational rearrangements in the protein by reversing Mg(2+)-induced changes in Trp fluorescence and surface hydrophobicity. In a larger physiological perspective, exchanging or replacing Mg(2+) with Ca(2+) reduces the Ca(2+)-binding ...Continue Reading

References

May 1, 1980·Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Für Klinische Chemie Und Klinische Biochemie·H Ebel, T Günther
Jun 1, 1995·Protein Science : a Publication of the Protein Society·S Linse, W J Chazin
Sep 1, 1995·Nature Structural Biology·H KuboniwaA Bax
Aug 1, 1994·Quarterly Reviews of Biophysics·J J FalkeO B Peersen
Jun 1, 1997·Protein Science : a Publication of the Protein Society·M AnderssonL A Svensson
Aug 1, 1997·Nature Structural Biology·B A SchulmanC Redfield
Jul 17, 1998·Current Opinion in Chemical Biology·J EvenäsS Forsén
Oct 24, 1998·The Journal of Biological Chemistry·A MalmendalS Forsén
Jan 8, 1999·Journal of Molecular Biology·D AlloucheY H Sanejouand
Oct 8, 1999·Biochemistry·A MalmendalT Drakenberg
Feb 24, 2001·Protein Science : a Publication of the Protein Society·S R MartinP M Bayley
May 30, 2002·The Journal of Biological Chemistry·Schuichi KoizumiAndreas Jeromin
Feb 20, 2003·Protein Science : a Publication of the Protein Society·Hanudatta S AtreyaClaudio Luchinat
Mar 13, 2003·Chemical Reviews·Todor Dudev, Carmay Lim
Jul 24, 2003·Bulletin of Mathematical Biology·Hui-Chih HungGu-Gang Chang
Jul 31, 2003·Biochemical Society Transactions·S Hilfiker
Dec 19, 2003·Protein Expression and Purification·Ming LiJan-Christer Janson
Mar 30, 2004·Trends in Neurosciences·Robert D BurgoyneAlexei V Tepikin
Apr 23, 2004·The Journal of Biological Chemistry·Andreas JerominYogendra Sharma
Mar 5, 2005·The Journal of Biological Chemistry·Masanori OsawaJames B Ames
Sep 9, 2005·The Journal of Biological Chemistry·Jennifer N WingardJames B Ames
Mar 22, 2006·The Journal of Cell Biology·Tomoe Y NakamuraJunichi Nabekura
Jun 29, 2006·Journal of Biomolecular NMR·Sulakshana MukherjeeKandala V R Chary
Feb 22, 2007·Nature Reviews. Neuroscience·Robert D Burgoyne
Jun 26, 2007·The Biochemical Journal·Jessica L GiffordHans J Vogel

❮ Previous
Next ❯

Citations

May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Marina MikhaylovaMichael R Kreutz
Aug 3, 2011·The Journal of Biological Chemistry·Jennifer H BenbowBarbara E Ehrlich
Sep 19, 2012·The Journal of Biological Chemistry·Jennifer H BenbowBarbara E Ehrlich
Sep 20, 2012·The Journal of Biological Chemistry·Hannah V McCueLee P Haynes
Jul 30, 2010·Cold Spring Harbor Perspectives in Biology·Hannah V McCueRobert D Burgoyne
Jul 25, 2014·PloS One·Pasham Parameshwar ReddyMichael R Kreutz
Aug 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pétur O HeidarssonCiro Cecconi
Sep 22, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Kousik ChandraK V R Chary
Dec 27, 2015·Colloids and Surfaces. B, Biointerfaces·Samuel LemireÉlodie Boisselier
Jan 30, 2015·Protein Science : a Publication of the Protein Society·Khoa PhamJaroslava Miksovska
Dec 10, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ku-Chung ChenLong-Sen Chang
Jul 5, 2011·Journal of Neurochemistry·Marina MikhaylovaMichael R Kreutz
Mar 10, 2010·Journal of Molecular Recognition : JMR·Robert J FalconerBrett M Collins
Jan 8, 2010·Protein Science : a Publication of the Protein Society·Hao HuangHans J Vogel
May 24, 2015·Biochimica Et Biophysica Acta·Evgeni Yu ZerniiKarl-W Koch
Nov 18, 2014·Frontiers in Cellular Neuroscience·Arthur P H de Jong, Diasynou Fioravante
Mar 6, 2019·Cold Spring Harbor Perspectives in Biology·Robert D BurgoyneLee P Haynes
Dec 1, 2019·The FEBS Journal·Elisa Millana FañanásAndrea Mattevi
Sep 6, 2019·Cellular and Molecular Life Sciences : CMLS·Min-Jeong KangJoong-Soo Han
Sep 17, 2020·Cellular and Molecular Life Sciences : CMLS·Lasse StabyBirthe B Kragelund
Jan 9, 2019·Frontiers in Molecular Neuroscience·Philipp O TsvetkovEvgeni Yu Zernii
Mar 23, 2019·Frontiers in Molecular Neuroscience·Valerio Marino, Daniele Dell'Orco
Jan 16, 2010·Biochemical Society Transactions·Marina MikhaylovaMichael R Kreutz
Feb 6, 2019·Molecular Neurobiology·Julia Bandura, Zhong-Ping Feng
Jan 9, 2019·Frontiers in Molecular Neuroscience·Dhawal ChoudharyCiro Cecconi
Jul 18, 2021·Biochemical and Biophysical Research Communications·Regur PhanindranathYogendra Sharma
Jul 19, 2008·Protein Expression and Purification·Dan A De CotiisJohn M Flanagan
Aug 12, 2008·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Mifang YangChangliang Zhu
Jan 27, 2009·Biochimica Et Biophysica Acta·Ghazaleh TazminiRobert J Kay
Sep 10, 2013·Structure·Pétur O HeidarssonCiro Cecconi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.