Binding of the periplakin linker requires vimentin acidic residues D176 and E187
Por:
Odintsova, Elena, Mohammed, Fiyaz, Trieber, Catharine, Rodriguez-Zamora, Penelope, Al-Jassar, Caezar, Huang T.-H., Fogl, Claudia, Knowles, Timothy, Sridhar, Pooja, Kumar, Jitendra, Jeeves, Mark, Chidgey, Martyn, Overduin, Michael
Publicada:
1 ene 2020
Resumen:
Plakin proteins form connections that link the cell membrane to the intermediate filament cytoskeleton. Their interactions are mediated by a highly conserved linker domain through an unresolved mechanism. Here analysis of the human periplakin linker domain structure reveals a bi-lobed module transected by an electropositive groove. Key basic residues within the periplakin groove are vital for co-localization with vimentin in human cells and compromise direct binding which also requires acidic residues D176 and E187 in vimentin. We propose a model whereby basic periplakin linker domain residues recognize acidic vimentin side chains and form a complementary binding groove. The model is shared amongst diverse linker domains and can be used to investigate the effects of pathogenic mutations in the desmoplakin linker associated with arrhythmogenic right ventricular cardiomyopathy. Linker modules either act solely or collaborate with adjacent plakin repeat domains to create strong and adaptable tethering within epithelia and cardiac muscle.
Filiaciones:
Odintsova, Elena:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Mohammed, Fiyaz:
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England
Trieber, Catharine:
Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, 474 Medical Sciences Building, Edmonton, AB T6G 2H7, Canada
Univ Alberta, Fac Med & Dent, Dept Biochem, 474 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada
Rodriguez-Zamora, Penelope:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Instituto de Fisica, Universidad Nacional Autonoma de MexicoMexico City 04510, Mexico
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Univ Nacl Autonoma Mexico, Inst Fis, Mexico City 04510, DF, Mexico
Al-Jassar, Caezar:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Huang T.-H.:
School of Biosciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Fogl, Claudia:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Binding Site, Birmingham, B15 1QT, United Kingdom
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Binding Site, Birmingham B15 1QT, W Midlands, England
Knowles, Timothy:
School of Biosciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England
Sridhar, Pooja:
School of Biosciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England
Kumar, Jitendra:
Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, 474 Medical Sciences Building, Edmonton, AB T6G 2H7, Canada
Univ Alberta, Fac Med & Dent, Dept Biochem, 474 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada
Jeeves, Mark:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Chidgey, Martyn:
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Institute of Clinical Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England
Univ Birmingham, Inst Clin Sci, Birmingham B15 2TT, W Midlands, England
Overduin, Michael:
Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, 474 Medical Sciences Building, Edmonton, AB T6G 2H7, Canada
Univ Alberta, Fac Med & Dent, Dept Biochem, 474 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada
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