Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca(2+)-dependent, low-affinity trans-interaction.
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.
Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, Würzburg, D-97070, Germany.
Jens
J
Waschke
Carlos
C
Menendez-Castro
Paola
P
Bruggeman
Rainer
R
Koob
Masayuki
M
Amagai
Hermann J
HJ
Gruber
Detlev
D
Drenckhahn
Werner
W
Baumgartner
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D051183:Desmoglein 1 / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D011487:Protein Conformation / Q000187:drug effects
D051183:Desmoglein 1; D002118:Calcium