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PMID: 17009962 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site.

The Biochemical journal ·Vol. 401 ·No. 3 ·2007-02-01 ·Pages 667-77

Hnia K, Zouiten D, Cantel S, Chazalette D, Hugon G, Fehrentz JA, Masmoudi A, Diment A, Bramham J, Mornet D, Winder SJ

Abstract

Dystrophin forms part of a vital link between actin cytoskeleton and extracellular matrix via the transmembrane adhesion receptor dystroglycan. Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan via their highly conserved C-terminal cysteine-rich regions, comprising the WW domain (protein-protein interaction domain containing two conserved tryptophan residues), EF hand and ZZ domains. The EF hand region stabilizes the WW domain providing the main interaction site between dystrophin or utrophin and dystroglycan. The ZZ domain, containing a predicted zinc finger motif, stabilizes the WW and EF hand domains and strengthens the overall interaction between dystrophin or utrophin and beta-dystroglycan. Using bacterially expressed ZZ domain, we demonstrate a conformational effect of zinc binding to the ZZ domain, and identify two zinc-binding regions within the ZZ domain by SPOTs overlay assays. Epitope mapping of the dystrophin ZZ domain was carried out with new monoclonal antibodies by ELISA, overlay assay and immunohistochemistry. One monoclonal antibody defined a discrete region of the ZZ domain that interacts with beta-dystroglycan. The epitope was localized to the conformationally sensitive second zinc-binding site in the ZZ domain. Our results suggest that residues 3326-3332 of dystrophin form a crucial part of the contact region between dystrophin and beta-dystroglycan and provide new insight into ZZ domain organization and function.

MeSH Terms
Amino Acid Sequence Binding Sites Dystroglycans/chemistry,metabolism Dystrophin/chemistry,genetics,metabolism Molecular Sequence Data Mutation, Missense Protein Binding Protein Structure, Tertiary Utrophin/chemistry,metabolism Zinc/chemistry,metabolism
Chemicals
Dystrophin Utrophin Dystroglycans Zinc
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hnia Karim
Université Montpellier 1, Unité de Formation et de Recherche de Médecine, Laboratoire de Physiologie des Interactions, Institut de Biologie, Boulevard Henri IV, F-34062, France.
Zouiten Dora
Cantel Sonia
Chazalette Delphine
Hugon Gérald
Fehrentz Jean-Alain
Masmoudi Ahmed
Diment Ann
Bramham Janice
Mornet Dominique
Winder Steve J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20061051
Published
2007-02-01
Pages
667-77
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1770854
Subset
IM
Grants
Wellcome Trust · 042180 · United Kingdom
External Links
PubMed source DOI: 10.1042/BJ20061051 PMC Full Text View journal details
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