Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca(2+)-dependent, low-affinity trans-interaction.

Abstract

Desmoglein 1 is a desmosomal member of the cadherin family expressed in stratified epithelia. Desmoglein 1 is the target adhesion molecule of severe blistering skin diseases such as pemphigus or bullous impetigo. However, despite this enormous pathological relevance, the molecular binding properties of desmoglein 1 are largely unknown. Using atomic force microscopic imaging, we found that desmoglein 1 molecules displayed Ca(2+)-dependent conformational changes of the extracellular domains. By single-molecule force-distance cycles, we provide evidence that desmoglein 1 undergoes Ca(2+)-dependent (K (d) = 0.8 mM Ca(2+)) homophilic trans-interaction, which is highly relevant for the contribution of desmoglein 1 homophilic binding to keratinocyte cohesion in distinct epidermal layers. Moreover, while the single-unit unbinding force is comparable to other cadherins (approximately 40 pN at retrace velocity of 300 nm/s), apparent differences with respect to multivalency of interaction and lifetime of single bonds (0.17 s) were observed. Thus, besides the biophysical characterization of desmoglein 1, a main outcome of the study is that desmoglein 1 differs from other members of the cadherin family in terms of some molecular binding properties.

• Authors: Jens Waschke, Carlos Menendez-Castro, Paola Bruggeman, Rainer Koob, Masayuki Amagai, Hermann J Gruber, Detlev Drenckhahn, Werner Baumgartner
• Journal: The Journal of membrane biology (J Membr Biol) Vol. 216 Issue 2-3 Pg. 83-92 (Apr 2007) ISSN: 0022-2631 [Print] United States
• PMID: 17657525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Desmoglein 1
• Calcium

Topics

• Animals
• CHO Cells
• Calcium (pharmacology)
• Cricetinae
• Cricetulus
• Desmoglein 1 (chemistry)
• Microscopy, Atomic Force
• Protein Conformation (drug effects)