7A7D

Cadherin fit into cryo-ET map

This is a non-PDB format compatible entry.

Summary for 7A7D

• Entry DOI: 10.2210/pdb7a7d/pdb
• EMDB information: 11678
• Descriptor: Desmoglein-2, Desmocollin-2 (2 entities in total)
• Functional Keywords: cadherin, desmosome, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 14
• Total formula weight: 859341.96

Authors

Sikora, M.,Ermel, U.H.,Seybold, A.,Kunz, M.,Calloni, G.,Reitz, J.,Vabulas, R.M.,Hummer, G.,Frangakis, A.S. (deposition date: 2020-08-28, release date: 2020-12-23)

Primary citation

Sikora, M.,Ermel, U.H.,Seybold, A.,Kunz, M.,Calloni, G.,Reitz, J.,Vabulas, R.M.,Hummer, G.,Frangakis, A.S.
Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography.
Proc.Natl.Acad.Sci.USA, 117:27132-27140, 2020

PubMed Abstract: Desmosomes are cell-cell junctions that link tissue cells experiencing intense mechanical stress. Although the structure of the desmosomal cadherins is known, the desmosome architecture-which is essential for mediating numerous functions-remains elusive. Here, we recorded cryo-electron tomograms (cryo-ET) in which individual cadherins can be discerned; they appear variable in shape, spacing, and tilt with respect to the membrane. The resulting sub-tomogram average reaches a resolution of ∼26 Å, limited by the inherent flexibility of desmosomes. To address this challenge typical of dynamic biological assemblies, we combine sub-tomogram averaging with atomistic molecular dynamics (MD) simulations. We generate models of possible cadherin arrangements and perform an in silico screening according to biophysical and structural properties extracted from MD simulation trajectories. We find a truss-like arrangement of cadherins that resembles the characteristic footprint seen in the electron micrograph. The resulting model of the desmosomal architecture explains their unique biophysical properties and strength.

PubMed: 33067392
DOI: 10.1073/pnas.2004563117

Experimental method

ELECTRON MICROSCOPY (26 Å)