title: Crystal structure of a rigid four-spectrin-repeat fragment of the human desmoplakin plakin domain.
abstract: The plakin protein family serves to connect cell-cell and cell-matrix adhesion molecules to the intermediate filament cytoskeleton. Desmoplakin (DP) is an integral part of desmosomes, where it links desmosomal cadherins to the intermediate filaments. The 1056-amino-acid N-terminal region of DP contains a plakin domain common to members of the plakin family. Plakin domains contain multiple copies of spectrin repeats (SRs). We determined the crystal structure of a fragment of DP, residues 175-630, consisting of four SRs and an inserted SH3 domain. The four repeats form an elongated, rigid structure. The SH3 domain is present in a loop between two helices of an SR and interacts extensively with the preceding SR in a manner that appears to limit inter-repeat flexibility. The intimate intramolecular association of the SH3 domain with the preceding SR is also observed in plectin, another plakin protein, but not in α-spectrin, suggesting that the SH3 domain of plakins contributes to the stability and rigidity of this subfamily of SR-containing proteins.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods*; D051180:Desmoplakins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry*; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains
chemical_list: D051180:Desmoplakins; D013049:Spectrin