The three-dimensional molecular structure of the desmosomal plaque

• DOI: 10.1073/pnas.1019469108
• Publication Date: 2011-04-05T03:19:19Z
• Authors: Ashraf Al-Amoudi; Daniel Castaño-Diez; Damien P. Devos; Robert B. Russell; Graham T. Johnson; Achilleas S. Fran...
• Keywords: Plakoglobin; Desmoplakin; Desmosome

The cytoplasmic surface of intercellular junctions is a complex network molecular interactions that link the extracellular region desmosomal cadherins with cytoskeletal intermediate filaments. Although 3D structures major plaque components are known, overall architecture remains unknown. We used cryoelectron tomography vitreous sections from human epidermis to record images desmosomes in vivo and situ at resolution. Our results show desmosome 2D interconnected quasiperiodic lattice, similar spatial organization side. Subtomogram averaging reveals two distinct layers plaque: low-density layer closer membrane high-density further away membrane. When combined heuristic, allowing simultaneous constrained fitting high-resolution proteins (desmoplakin, plakophilin, plakoglobin), it their mutual explains stoichiometry. arrangement suggests alternate plakoglobin–desmoplakin complexes create template on which cluster before they stabilize extracellularly by binding N-terminal tips. Plakophilins added as reinforcement fill gap between formed plasma