Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure.
Desmosomes are intercellular junctions in which cadherin cell adhesion molecules are linked to the intermediate filament (IF) system. Desmoplakin is a member of the plakin family of IF-binding proteins. The C-terminal domain of desmoplakin (DPCT) mediates binding to IFs in desmosomes. The DPCT sequence contains three regions, termed A, B and C, consisting of 4.5 copies of a 38-amino acid repeat motif. We demonstrate that these regions form discrete subdomains that bind to IFs and report the crystal structures of domains B and C. In contrast to the elongated structures formed by other kinds of repeat motifs, the plakin repeats form a globular structure with a unique fold. A conserved basic groove found on the domain may represent an IF-binding site.
Choi
Hee-Jung
HJ
Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, California 94305, USA.
Park-Snyder
Shaun
S
Pascoe
Lauren T
LT
Green
Kathleen J
KJ
Weis
William I
WI
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051180:Desmoplakins; D006801:Humans; D066298:In Vitro Techniques; D007382:Intermediate Filaments / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010449:Peptide Mapping; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D010446:Peptide Fragments; D011994:Recombinant Proteins