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

Area of Science:

• Cell Biology
• Biophysics
• Dermatology

Background:

• Desmoglein 1 (DSG1) is a crucial cadherin in stratified epithelia.
• DSG1 is the primary target in blistering diseases like pemphigus and bullous impetigo.
• The molecular binding properties of DSG1 remain largely uncharacterized despite its pathological significance.

Purpose of the Study:

• To investigate the molecular binding properties of Desmoglein 1.
• To elucidate the role of calcium ions in DSG1 interactions.
• To compare DSG1's binding characteristics with other cadherins.

Main Methods:

• Atomic force microscopy (AFM) for molecular imaging.
• Single-molecule force spectroscopy using force-distance cycles.
• Analysis of Ca(2+)-dependent conformational changes and homophilic trans-interaction.

Main Results:

• DSG1 exhibits Ca(2+)-dependent conformational changes in its extracellular domains.
• Evidence of Ca(2+)-dependent homophilic trans-interaction with a dissociation constant (K(d)) of 0.8 mM Ca(2+).
• DSG1 shows comparable unbinding forces to other cadherins but differs in multivalency and bond lifetime (0.17 s).

Conclusions:

• DSG1's Ca(2+)-dependent binding is vital for keratinocyte cohesion in the epidermis.
• DSG1 possesses unique molecular binding properties distinct from other cadherin family members.
• This study provides critical biophysical insights into DSG1 function and its role in skin integrity.