TY - JOUR
T1 - The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins
AU - Harrison, Oliver J.
AU - Jin, Xiangshu
AU - Hong, Soonjin
AU - Bahna, Fabiana
AU - Ahlsen, Goran
AU - Brasch, Julia
AU - Wu, Yinghao
AU - Vendome, Jeremie
AU - Felsovalyi, Klara
AU - Hampton, Cheri M.
AU - Troyanovsky, Regina B.
AU - Ben-Shaul, Avinoam
AU - Frank, Joachim
AU - Troyanovsky, Sergey M.
AU - Shapiro, Lawrence
AU - Honig, Barry
N1 - Funding Information:
We are thankful to Dr. J. K. Wahl (University of Nebraska) for providing A-431D cells. This work has been supported by grants from the National Institutes of Health (AR44016-04 to S.M.T., R01 GM062270 to L.S., and T32 GM082797 to B.H.) and from the National Science Foundation (MCB-0918535 to B.H.). The financial support of the US-Israel Binational Science Foundation (grant 2006-401 to A.B.-S., B.H., and L.S.) and the Israel Science Foundation (grant 659/06 to A.B.-S.) is gratefully acknowledged. X-ray data were acquired at the X4A and X4C beamlines of the National Synchrotron Light Source, Brookhaven National Laboratory; the beamlines are operated by the New York Structural Biology Center.
PY - 2011/2/9
Y1 - 2011/2/9
N2 - Adherens junctions, which play a central role in intercellular adhesion, comprise clusters of type I classical cadherins that bind via extracellular domains extended from opposing cell surfaces. We show that a molecular layer seen in crystal structures of E- and N-cadherin ectodomains reported here and in a previous C-cadherin structure corresponds to the extracellular architecture of adherens junctions. In all three ectodomain crystals, cadherins dimerize through a trans adhesive interface and are connected by a second, cis, interface. Assemblies formed by E-cadherin ectodomains coated on liposomes also appear to adopt this structure. Fluorescent imaging of junctions formed from wild-type and mutant E-cadherins in cultured cells confirm conclusions derived from structural evidence. Mutations that interfere with the trans interface ablate adhesion, whereas cis interface mutations disrupt stable junction formation. Our observations are consistent with a model for junction assembly involving strong trans and weak cis interactions localized in the ectodomain.
AB - Adherens junctions, which play a central role in intercellular adhesion, comprise clusters of type I classical cadherins that bind via extracellular domains extended from opposing cell surfaces. We show that a molecular layer seen in crystal structures of E- and N-cadherin ectodomains reported here and in a previous C-cadherin structure corresponds to the extracellular architecture of adherens junctions. In all three ectodomain crystals, cadherins dimerize through a trans adhesive interface and are connected by a second, cis, interface. Assemblies formed by E-cadherin ectodomains coated on liposomes also appear to adopt this structure. Fluorescent imaging of junctions formed from wild-type and mutant E-cadherins in cultured cells confirm conclusions derived from structural evidence. Mutations that interfere with the trans interface ablate adhesion, whereas cis interface mutations disrupt stable junction formation. Our observations are consistent with a model for junction assembly involving strong trans and weak cis interactions localized in the ectodomain.
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U2 - 10.1016/j.str.2010.11.016
DO - 10.1016/j.str.2010.11.016
M3 - Article
C2 - 21300292
AN - SCOPUS:79551699994
SN - 0969-2126
VL - 19
SP - 244
EP - 256
JO - Structure
JF - Structure
IS - 2
ER -