TY - JOUR
T1 - Structural and biophysical characterization of the type VII collagen vWFA2 subdomain leads to identification of two binding sites
AU - Gebauer, Jan M.
AU - Flachsenberg, Florian
AU - Windler, Cordula
AU - Richer, Barbara
AU - Baumann, Ulrich
AU - Seeger, Karsten
N1 - Funding Information:
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.
Publisher Copyright:
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081716457&partnerID=8YFLogxK
U2 - 10.1002/2211-5463.12807
DO - 10.1002/2211-5463.12807
M3 - Journal articles
C2 - 32031736
AN - SCOPUS:85081716457
SN - 2211-5463
VL - 10
SP - 580
EP - 592
JO - FEBS Open Bio
JF - FEBS Open Bio
IS - 4
ER -
