http://www.cnr.it/ontology/cnr/individuo/prodotto/ID17680
Mutagenesis at the alpha-beta interface impairs the cleavage of the dystroglycan precursor (Articolo in rivista)
- Type
- Label
- Mutagenesis at the alpha-beta interface impairs the cleavage of the dystroglycan precursor (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Alternative label
Sciandra F., Bozzi M., Morlacchi S., Galtieri A., Giardina B., Brancaccio A. (2009)
Mutagenesis at the alpha-beta interface impairs the cleavage of the dystroglycan precursor
in The FEBS journal (Print)
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- Sciandra F., Bozzi M., Morlacchi S., Galtieri A., Giardina B., Brancaccio A. (literal)
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- Sciandra F.; Giardina B.; Brancaccio A.: Istituto di chimica del riconoscimento molecolare, CNR
Bozzi M.: Istituto di biochimica e biochimica clinica, UCSC
Morlacchi S.: Dipartimento di Biologia Animale ed Ecologia Marina, Universita` degli Studi di Messina
Galtieri A: Dipartimento di Chimica Organica e Biologica, Universita` di Messina (literal)
- Titolo
- Mutagenesis at the alpha-beta interface impairs the cleavage of the dystroglycan precursor (literal)
- Abstract
- The interaction between alpha-dystroglycan (alpha-DG) and beta-dystroglycan (beta-DG),
the two constituent subunits of the adhesion complex dystroglycan, is crucial
in maintaining the integrity of the dystrophin-glycoprotein complex. The
importance of the alpha-beta interface can be seen in the skeletal muscle of humans
affected by severe conditions, such as Duchenne muscular dystrophy, where
the alpha-beta interaction can be secondarily weakened or completely lost, causing
sarcolemmal instability and muscular necrosis. The reciprocal binding epitopes
of the two subunits reside within the C-terminus of alpha-DG and the
ectodomain of beta-DG. As no ultimate structural data are yet available on the
alpha-beta interface, site-directed mutagenesis was used to identify which specific
amino acids are involved in the interaction. A previous alanine-scanning
analysis of the recombinant beta-DG ectodomain allowed the identification of
two phenylalanines important for alpha-DG binding, namely F692 and F718. In
this article, similar experiments performed on the alpha-DG C-terminal domain
pinpointed two residues, G563 and P565, as possible binding counterparts
of the two beta-DG phenylalanines. In 293-Ebna cells, the introduction of alanine
residues instead of F692, F718, G563 and P565 prevented the cleavage
of the DG precursor that liberates alpha- and beta-DG, generating a pre-DG of
about 160 kDa. This uncleaved pre-DG tetramutant is properly targeted at
the cell membrane, is partially glycosylated and still binds laminin in pulldown
assays. These data reinforce the notion that DG processing and its
membrane targeting are two independent processes, and shed new light on
the molecular mechanism that drives the maturation of the DG precursor. (literal)
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