Abstract
The interaction between α-actinin and titin, two modular muscle proteins, is essential for sarcomere assembly. We have solved the solution structure of a complex between the calcium-insensitive C-terminal EF-hand domain of α-actinin-2 and the seventh Z-repeat of titin. The structure of the complex is in a semi-open conformation and closely resembles that of myosin light chains in their complexes with heavy chain IQ motifs. However, no IQ motif is present in the Z-repeat, suggesting that the semi-open conformation is a general structural solution for calcium-independent recognition of EF-hand domains.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Slupsky, C.M. & Sykes, B.D. In Calcium as a cellular regulator (eds Carafoli, E. & Klee, C.B.) 73–99 (Oxford University Press, New York; 1999)
Ikura, M. Trends Biochem. Sci. 21, 14–17 (1996).
Nakayama, S. & Kretsinger, R.H. Ann. Rev. Biophys. Biomol. Struct. 23, 473–507 (1994).
Blanchard, A., Ohanian, V. & Critchley, D. J. Muscle Res. Cell. Motil. 10, 280–289 (1989).
Beggs, A.H. et al. J. Biol. Chem. 267, 9281–9288 (1992).
Luther, P.K. J. Struct. Biol. 129, 1–16 (2000).
Maruyama, K. FASEB J. 11, 341–145 (1997).
Ohtsuka, H., Yajima, H., Maruyama, K. & Kimura, S. Biochem. Biophys. Res. Commun. 235, 1–3 (1997).
Sorimachi, H. et al. J. Mol. Biol. 270, 688–695 (1997).
Gautel, M., Goulding, D., Bullard, B., Weber, K. & Fürst, D.O. J. Cell Sci. 109, 2747–2754 (1996).
Young, P. & Gautel, M. EMBO J. 19, 6331–6340 (2000).
Joseph, C. et al. Biochemistry 40, 4957–4965 (2001).
Xie, X. et al. Nature 368, 306–312 (1994).
Houdusse, A. & Cohen, C. Structure 4, 21–32 (1996).
Swindells, M.B. & Ikura, M. Nature Struct. Biol. 3, 501–504 (1996).
Rhoads, A.R. & Friedberg, F. FASEB J. 11, 331–340 (1997).
Bayley, P.M., Findlay, W.A. & Martin, S.R. Protein Sci. 5, 1215–1228 (1996).
Atkinson, R.A. et al. Biochemistry 39, 5255–5264 (2000).
Vassylyev, D.G., Takeda, S., Wakatsuki, S., Maeda, K. & Maeda, Y. Proc. Natl. Acad. Sci. USA 95, 4847–4852 (1998).
Amodeo, P. et al. J. Mol. Biol. 306, 81–95 (2001).
Meador, W.E., Means, A.R. & Quiocho, F.A. Science 262, 1718–1721 (1993).
Schumacher, M.A., Rivard, A.F., Bachinger, H.P. & Adelman, J.P. Nature 410, 1120–1124 (2001).
Nelson, M.R. & Chazin, W.J. Protein Sci. 7, 270–282 (1998).
Lee, A.L., Kinnear, S.A. & Wand, J. Nature Struct. Biol. 7, 72–78 (2000).
Atkinson, R.A. et al. J. Biomol. NMR 16, 277–278 (2000).
Delaglio, F., Grzesiek, S., Vuister, G., Zhu, G., Pfeifer, J. & Bax, A. J. Biomol. NMR 6, 277–293 (1995).
Bartels, C., Xia, T.-H., Billeter, M., Güntert, P. & Wüthrich, K. J. Biomol. NMR 5, 1–10 (1995).
Cornilescu, G., Delaglio, F. & Bax, A. J. Biomol. NMR 13, 289–302 (1999).
Güntert, P., Mumenthaler, C. & Wüthrich, K. J. Mol. Biol. 273, 283–298 (1997).
Brünger, A. X-PLOR Software Manual, version 3.1 (Yale University Press, New Haven; 1992).
Laskowski, R.A., Rullmann, J.A.C., MacArthur, M.W., Kaptein, R. & Thornton, J.M. J. Biomol. NMR 8, 477–486 (1996).
Sippl, M J. Proteins 17, 355–362 (1993).
Vriend, G. & Sander, C. J. Appl. Crystallogr. 26, 47–60 (1993).
Acknowledgements
The authors wish to thank G. Stier for help in protein production at the early stage of the project, and R. Biekofsky and J. Feeney for helpful discussions. The National 800 MHz NMR facility in Cambridge is supported by the BBSRC and the Wellcome Trust. This work is dedicated to the memory of Matti Saraste.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Atkinson, R., Joseph, C., Kelly, G. et al. Ca2+-independent binding of an EF-hand domain to a novel motif in the α-actinin–titin complex. Nat Struct Mol Biol 8, 853–857 (2001). https://doi.org/10.1038/nsb1001-853
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nsb1001-853
This article is cited by
-
Lipid droplets contribute myogenic differentiation in C2C12 by promoting the remodeling of the acstin-filament
Cell Death & Disease (2021)
-
Mislocalization of SMN from the I-band and M-band in human skeletal myofibers in spinal muscular atrophy associates with primary structural alterations of the sarcomere
Cell and Tissue Research (2020)
-
Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains
Scientific Reports (2017)
-
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1
Scientific Reports (2016)
-
Chemical shift assignments of the C-terminal EF-hand domain of α-actinin-1
Biomolecular NMR Assignments (2016)