Abstract
The NMR high-resolution structure of calmodulin complexed with a fragment of the olfactory cyclic-nucleotide gated channel is described. This structure shows features that are unique for this complex, including an active role of the linker connecting the N- and C-lobes of calmodulin upon binding of the peptide. Such linker is not only involved in the formation of an hydrophobic pocket to accommodate a bulky peptide residue, but it also provides a positively charged region complementary to a negative charge of the target. This complex of calmodulin with a target not belonging to the kinase family was used to test the residual dipolar coupling (RDC) approach for the determination of calmodulin binding modes to peptides. Although the complex here characterized belongs to the (1--14) family, high Q values were obtained with all the 1:1 complexes for which crystalline structures are available. Reduction of the RDC data set used for the correlation analysis to structured regions of the complex allowed a clear identification of the binding mode. Excluded regions comprise calcium binding loops and loops connecting the EF-hand motifs.
Similar content being viewed by others
References
I. André T. Kesvatera B. Jonsson K.S. Akerfeldt S. Linse (2004) Biophys. J. 87 1929–1938
M. Aoyagi A.S. Arvai J.A. Tainer E.D. Getzoff (2003) EMBO J. 22 766–75
Y.S. Babu C.E. Bugg W.J. Cook (1988) J. Mol. Biol. 204 191–204
G. Barbato M. Ikura L.E. Kay R.W. Pastor A. Bax (1992) Biochemistry 31 5269–5278
A. Bax (2003) Protein Sci. 12 1–16
A. Bax G. Kontaxis N. Tjandra (2001) Methods Enzymol. 339 127–174
C.A. Bewley K.R. Gustafson M.R. Boyd D.G. Covell A. Bax G.M. Clore A.M. Gronenborn (1998) Nat. Struct. Biol. 5 571–578
Brunger, A.T. (1992) Yale University Press, New Haven.
D.L. Bryce A. Bax (2004) J. Biomol. NMR. 28 273–87
J.J. Chou S. Li C.B. Klee A. Bax (2001) Nat. Struct. Biol. 8 990–997
G.M. Clore P.C. Driscoll P.T. Wingfield A.M. Gronenborn (1990a) Biochemistry 29 7387–7401
Clore, G.M., Szabo, A., Bax, A., Kay, L.E., Driscoll, P.C. and Gronenborn, A.M. (1990b) J. Am. Chem. Soc. 4989–4991
G.M. Clore A.M. Gronenborn (1998) Proc. Natl. Acad. Sci. USA 95 5891–5898
G.M. Clore A.M. Gronenborn N. Tjandra (1998) J. Magn. Reson. 131 159–162
G.M. Clore D.S. Garrett (1999) J. Am. Chem. Soc. 121 9008–9012
G. Cornilescu J.L. Marquardt M. Ottiger A. Bax (1998) J. Am. Chem. Soc. 120 6836–6837
F. Delaglio S. Grzesiek G.W. Vuister G. Zhu J. Pfeifer A. Bax (1995) J. Biomol. NMR 6 277–293
N. Farrow D.R. Muhandiram A.U. Singer S.M. Pascal C.M. Kay G. Gish S.E. Shoelson T. Pawson J.D. Forman-Kay L.E. Kay (1994) Biochemistry 33 5984–600
M.W. Fischer J.A. Losonczi J.L. Weaver J.H. Prestegard (1999) Biochemistry 38 9013–9022
M.R. Hansen L. Mueller A. Pardi (1998) Nat. Struct. Biol. 5 1065–1074
M. Ikura G.M. Clore A.M. Gronenborn G. Zhu C.B. Klee A. Bax (1992) Science 256 632–638
M. Ikura A. Bax (1992) J. Am. Chem. Soc. 114 2433–2440
B. Johnson R.A. Blevins (1994) J. Biomol. NMR 4 603–614
L.E. Kay D.A. Torchia A. Bax (1989) Biochemistry 28 8972–8979
H. Kurokawa M. Osawa H. Kurihara N. Katayama H. Tokumitsu M.B. Swindells M. Kainosho M. Ikura (2001) J. Mol. Biol. 312 59–68
R.A. Laskowski J.A. Rullmannn M.W. MacArthur R. Kaptein J.M. Thornton (1996) J. Biomol. NMR 8 477–86
W. Lee M.J. Revington C. Arrowsmith L.E. Kay (1994) FEBS Lett. 350 87–90
G. Lipari A. Szabo (1982) J. Am. Chem. Soc. 104 4546–4559
M. Liu T.-Y. Chen B. Ahamed J. Li K.-W. Yau (1994) Science 266 1348–1354
J.A. Losonczi M. Andrec M.W. Fischer J.H. Prestegard (1999) J. Magn. Reson. 138 334–342
T.K. Mal N.R. Skrynnikov K.L. Yap L.E. Kay M. Ikura (2002) Biochemistry 41 12899–12906
W.E. Meador A.R. Means F.A. Quiocho (1992) Science 257 1251–1255
W.E. Meador A.R. Means F.A. Quiocho (1993) Science 262 1718–1721
R.S. Molday (1996) Curr. Opin. Neurobiol. 6 445–452
V.Y. Orekhov D.E. Nolde A.P. Golovanov P.M. Korzhnev A.S. Arseniev (1995) Appl. Magn. Reson. 9 581–588
M. Orsale S. Melino G.M. Contessa V. Torre G. Andreotti A. Motta M. Paci A. Desideri D.O. Cicero (2003) FEBS Lett. 548 11–16
M. Osawa H. Tokumitsu M.B. Swindells H. Kurihara M. Orita T. Shibanuma T. Furuya M. Ikura (1999) Nat. Struct. Biol. 6 819–824
M. Ottiger A. Bax (1999) J. Mol. Biol. 13 187–191
M. Ottiger F. Delaglio A. Bax (1997) J. Magn. Reson. 131 373–378
J.A. Putkey G.R. Slaughter A.R. Means (1985) J. Biol. Chem. 260 4704–4712
A.R. Rhoads F. Friedberg (1997) FASEB J. 11 331–340
N. Tjandra H. Kuboniwa H. Ren A. Bax (1995) Eur. J. Biochem. 230 1014–1024
N. Tjandra J.G. Omichinski A.M. Gronenborn G.M. Clore A. Bax (1997) Nat. Struct. Biol. 4 728–732
J.R. Tolman H.M. Al-Hashimi L.E. Kay J.H. Prestegard (2001) J. Am. Chem. Soc. 123 1416–1424
M.D. Varnum W.N. Zagotta (1997) Science 278 110–113
S.W. Vetter E. Leclerc (2003) Eur. J. Biochem. 270 404–414
K.L. Yap J. Kim K. Truong M. Sherman T. Yuan M. Ikura (2000) J. Struct. Funct. Genomics. 1 8–14
K.L. Yap T. Yuan T.K. Mal H.J. Vogel M. Ikura (2003) J. Mol. Biol. 328 193–204
M. Zweckstetter A. Bax (2000) J. Am. Chem. Soc. 122 3791–3792
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Contessa, G.M., Orsale, M., Melino, S. et al. Structure of calmodulin complexed with an olfactory CNG channelfragment and role of the central linker: Residual dipolar couplingsto evaluate calmodulin binding modes outside the kinase family. J Biomol NMR 31, 185–199 (2005). https://doi.org/10.1007/s10858-005-0165-1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10858-005-0165-1