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)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Sciandra F., Bozzi M., Morlacchi S., Galtieri A., Giardina B., Brancaccio A. (literal)
Pagina inizio
  • 4933 (literal)
Pagina fine
  • 4945 (literal)
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  • 276 (literal)
Rivista
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 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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