Open Access

ARTICLE

Forced Dissociation of the Strand Dimer Interface between C-Cadherin Ectodomains

by M.V. Bayas¹, K.Schulten², D. Leckb,³

1 Center for Biophysics and Computational Biology, UIUC, Urbana, IL, U.S.A.
2 Beckman Institute and Physics Department, Center for Biophysicsand Computational Biology, UIUC, Urbana, IL, U.S.A.
3 Chemical and Biomolecular Engineering, Center for Biophysicsand Computational Biology, UIUC, Urbana, IL, U.S.A.

Molecular & Cellular Biomechanics 2004, 1(2), 101-112. https://doi.org/10.3970/mcb.2004.001.101

Abstract

The force-induced dissociation of the strand dimer interface in C-cadherin has been studied using steered molecular dynamics simulations. The dissociation occurred, without domain unraveling, after the extraction of the conserved trypthophans (Trp2) from their respective hydrophobic pockets. The simulations revealed two stable positions for the Trp2 side chain inside the pocket. The most internal stable position involved a hydrogen bond between the ring Ne of Trp2 and the backbone carbonyl of Glu90. In the second stable position, the aromatic ring is located at the pocket entrance. After extracting the two tryptophans from their pockets, the complex exists in an intermediate bound state that involves a close packing of the tryptophans with residues Asp1 and Asp27 from both domains. Dissociation occurred after this residue association was broken. Simulations carried out with a complex formed between W2A mutants showed that the mutant complex dissociates more easily than the wild type complex does. These results correlate closely with the role of the conserved tryptophans suggested previously by site directed mutagenesis.

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Keywords

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