Jump to ContentJump to Main Navigation

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR increased in 2014: 3.268
Rank 106 out of 289 in category Biochemistry & Molecular Biology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

SCImago Journal Rank (SJR) 2014: 1.596
Source Normalized Impact per Paper (SNIP) 2014: 0.845
Impact per Publication (IPP) 2014: 2.992



The WW Domain of Dystrophin Requires EF-Hands Region to Interact with β-Dystroglycan

S. Rentschler / H. Linn / K. Deininger / M.T. Bedford / X. Espanel / M. Sudol

Citation Information: Biological Chemistry. Volume 380, Issue 4, Pages 431–442, ISSN (Print) 1431-6730, DOI: 10.1515/BC.1999.057, June 2005

Publication History

Published Online:


Skeletal muscle dystrophin is a 427 kDa protein thought to act as a link between the actin cytoskeleton and the extracellular matrix. Perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein β-dystroglycan, may lead to muscular dystrophy. Previously, the cysteine-rich region and first half of the carboxy-terminal domain of dystrophin were shown to interact with β-dystroglycan through a stretch of fifteen amino acids at the carboxy-terminus of β-dystroglycan. This region of dystrophin implicated in binding β-dystroglycan contains four modular protein domains: a WW domain, two putative Ca2+-binding EF-hand motifs, and a putative zinc finger ZZ domain. The WW domain is a globular domain of 38–40 amino acids with two highly conserved tryptophan residues spaced 20–22 amino acids apart. A subset of WW domains was shown to bind ligands that contain a Pro-Pro-x-Tyr core motif (where x is any amino acid). Here we elucidate the role of the WW domain of dystrophin and surrounding sequence in binding β-dystroglycan. We show that the WW domain of dystrophin along with the EF-hand motifs binds to the carboxy-terminus of β-dystroglycan. Through site-specific mutagenesis and in vitro binding assays, we demonstrate that binding of dystrophin to the carboxyterminus of β-dystroglycan occurs via a β-dystroglycan Pro-Pro-x-Tyr core motif. Targeted mutagenesis of conserved WW domain residues reveals that the dystrophin/β-dystroglycan interaction occurs primarily through the WW domain of dystrophin. Precise mapping of this interaction could aid in therapeutic design.

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Winston Chung and James T. Campanelli
Molecular Cell Biology Research Communications, 1999, Volume 2, Number 3, Page 162
Lucila S. Bruno, Xiaojing Li, Li Wang, Rodrigo V. Soares, Camille C. Siqueira, Frank G. Oppenheim, Robert F. Troxler, and Gwynneth D. Offner
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2005, Volume 1746, Number 1, Page 65
James M. Ervasti
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2007, Volume 1772, Number 2, Page 108
Valérie Bello, Nicole Moreau, Cathy Sirour, Magdalena Hidalgo, Nicolas Buisson, and Thierry Darribère
Developmental Biology, 2015, Volume 401, Number 1, Page 132
Hyung Min Jeong, Sung Ho Lee, Jinah Yum, Chang-Yeol Yeo, and Kwang Youl Lee
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2014, Volume 1843, Number 9, Page 2005
Adeline Vulin, Nicolas Wein, Dana M. Strandjord, Eric K. Johnson, Andrew R. Findlay, Baijayanta Maiti, Michael T. Howard, Yuuki J. Kaminoh, Laura E. Taylor, Tabatha R. Simmons, Will C. Ray, Federica Montanaro, Jim M. Ervasti, and Kevin M. Flanigan
Human Mutation, 2014, Volume 35, Number 2, Page 257
Bruno Constantin
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2014, Volume 1838, Number 2, Page 635
Arjan PM de Brouwer, Sander B Nabuurs, Ingrid EC Verhaart, Astrid R Oudakker, Roel Hordijk, Helger G Yntema, Jannet M Hordijk-Hos, Krysta Voesenek, Bert BA de Vries, Ton van Essen, Wei Chen, Hao Hu, Jamel Chelly, Johan T den Dunnen, Vera M Kalscheuer, Annemieke M Aartsma-Rus, Ben CJ Hamel, Hans van Bokhoven, and Tjitske Kleefstra
European Journal of Human Genetics, 2014, Volume 22, Number 4, Page 480
Elisabeth Le Rumeur, Jean-François Hubert, and Steve J. Winder
FEBS Letters, 2012, Volume 586, Number 17, Page 2717
Alice Tommasi di Vignano, Giovanni Di Zenzo, Marius Sudol, Gianni Cesareni, and Luciana Dente
FEBS Letters, 2000, Volume 471, Number 2-3, Page 229
Glen B. Legge, Maria A. Martinez-Yamout, David M. Hambly, Tam Trinh, Brian M. Lee, H. Jane Dyson, and Peter E. Wright
Journal of Molecular Biology, 2004, Volume 343, Number 4, Page 1081
Davin M. Henderson, Ava Yun Lin, David D. Thomas, and James M. Ervasti
Journal of Molecular Biology, 2012, Volume 416, Number 3, Page 414
Carlos G. García-Tovar, José Luna, Raúl Mena, Carlos I. Soto-Zárate, Rafael Cortés, Armando Pérez, Gloria León-Avila, Dominique Mornet, Alvaro Rendón, and José Manuel Hernández
Acta Histochemica, 2002, Volume 104, Number 3, Page 245
Virginie Carmignac and Madeleine Durbeej
The Journal of Pathology, 2012, Volume 226, Number 2, Page 200
Hitoshi Okazawa, Marius Sudol, and Tina Rich
Brain Research Bulletin, 2001, Volume 56, Number 3-4, Page 273
Melissa L.J. Rees, Chun-Fu Lien, and Dariusz C. Górecki
Neuromuscular Disorders, 2007, Volume 17, Number 2, Page 123
Karim Hnia, Jérôme Gayraud, Gérald Hugon, Michèle Ramonatxo, Sabine De La Porte, Stefan Matecki, and Dominique Mornet
The American Journal of Pathology, 2008, Volume 172, Number 6, Page 1509
Paloma Valverde
Biochemical and Biophysical Research Communications, 2000, Volume 276, Number 3, Page 990
Enrico Di Stasio, Francesca Sciandra, Bruno Maras, Francesca Di Tommaso, Tamara C. Petrucci, Bruno Giardina, and Andrea Brancaccio
Biochemical and Biophysical Research Communications, 1999, Volume 266, Number 1, Page 274
Aleksandr V Pereboev, Naseem Ahmed, Nguyen thi Man, and Glenn E Morris
Biochimica et Biophysica Acta (BBA) - General Subjects, 2001, Volume 1527, Number 1-2, Page 54
Michael J.F. Broderick and Steven J. Winder
Journal of Structural Biology, 2002, Volume 137, Number 1-2, Page 184
Mark F Mehler
Brain Research Reviews, 2000, Volume 32, Number 1, Page 277
Steven J Winder
Trends in Biochemical Sciences, 2001, Volume 26, Number 2, Page 118
Michael D Henry and Kevin P Campbell
Current Opinion in Cell Biology, 1999, Volume 11, Number 5, Page 602
Charles E Ganote and Stephen C Armstrong
The Lancet, 2002, Volume 359, Number 9310, Page 905
Masahiro Fukaya, Akifumi Kamata, Yoshinobu Hara, Hideaki Tamaki, Osamu Katsumata, Naoki Ito, Shin’ichi Takeda, Yutaka Hata, Tatsuo Suzuki, Masahiko Watanabe, Robert J. Harvey, and Hiroyuki Sakagami
Journal of Neurochemistry, 2011, Volume 116, Number 6, Page 1122
Zaidoun Salah, Rami Aqeilan, and Kay Huebner
Future Oncology, 2010, Volume 6, Number 2, Page 249
J. Giacomotto, C. Pertl, C. Borrel, M. C. Walter, S. Bulst, B. Johnsen, D. L. Baillie, H. Lochmuller, C. Thirion, and L. Segalat
Human Molecular Genetics, 2009, Volume 18, Number 21, Page 4089
Annemieke Aartsma-Rus, Judith C. T. Van Deutekom, Ivo F. Fokkema, Gert-Jan B. Van Ommen, and Johan T. Den Dunnen
Muscle & Nerve, 2006, Volume 34, Number 2, Page 135
Florian Toepert, José R. Pires, Christiane Landgraf, Hartmut Oschkinat, and Jens Schneider-Mergener
Angewandte Chemie, 2001, Volume 113, Number 5, Page 922

Comments (0)

Please log in or register to comment.