Abstract
Type VII collagen is an extracellular matrix protein, which is important for skin stability; however, detailed information at the molecular level is scarce. The second vWFA (von Willebrand factor type A) domain of type VII collagen mediates important interactions, and immunization of mice induces skin blistering in certain strains. To understand vWFA2 function and the pathophysiological mechanisms leading to skin blistering, we structurally characterized this domain by X-ray crystallography and NMR spectroscopy. Cell adhesion assays identified two new interactions: one with β1 integrin via its RGD motif and one with laminin-332. The latter interaction was confirmed by surface plasmon resonance with a KD of about 1 mm. These data show that vWFA2 has additional functions in the extracellular matrix besides interacting with type I collagen.
| Original language | English |
|---|---|
| Journal | FEBS Open Bio |
| Volume | 10 |
| Issue number | 4 |
| Pages (from-to) | 580-592 |
| Number of pages | 13 |
| DOIs | |
| Publication status | Published - 01.04.2020 |
Funding
This work was supported by the DFG Excellence Cluster ?Inflammation at Interfaces? (DFG 306/2); the SFB829 ?Molecular Mechanisms Regulating Skin Homeostasis? (SFB829/B11); and the research Training Group ?Modulation of Autoimmunity? (GRK1727). S. Leineweber is acknowledged for technical assistance. We thank the staff at the beamline ID29 at the European Synchrotron Radiation Facility (ESRF), Grenoble, France, for their support during data collection. Crystals were grown in the Cologne Crystallization facility (C2f; grant No. INST 216/682-1 FUGG from the German Research Foundation). R. Ludwig, K. Bieber, H. Iwata and S. Ibrahim are acknowledged for helpful discussion.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
