The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins

Oliver J. Harrison; Xiangshu Jin; Soonjin Hong; Fabiana Bahna; Goran Ahlsen; Julia Brasch; Yinghao Wu; Jeremie Vendome; Klara Felsovalyi; Cheri M. Hampton; Regina B. Troyanovsky; Avinoam Ben-Shaul; Joachim Frank; Sergey M. Troyanovsky; Lawrence Shapiro; Barry Honig

doi:10.1016/j.str.2010.11.016

The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins

Oliver J. Harrison, Xiangshu Jin, Soonjin Hong, Fabiana Bahna, Goran Ahlsen, Julia Brasch, Yinghao Wu, Jeremie Vendome, Klara Felsovalyi, Cheri M. Hampton, Regina B. Troyanovsky, Avinoam Ben-Shaul, Joachim Frank, Sergey M. Troyanovsky, Lawrence Shapiro, Barry Honig

Dermatology

Research output: Contribution to journal › Article › peer-review

320 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	244-256
Number of pages	13
Journal	Structure
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.str.2010.11.016
State	Published - Feb 9 2011

Funding

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.

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Access to Document

10.1016/j.str.2010.11.016

Cite this

Harrison, O. J., Jin, X., Hong, S., Bahna, F., Ahlsen, G., Brasch, J., Wu, Y., Vendome, J., Felsovalyi, K., Hampton, C. M., Troyanovsky, R. B., Ben-Shaul, A., Frank, J., Troyanovsky, S. M., Shapiro, L., & Honig, B. (2011). The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins. Structure, 19(2), 244-256. https://doi.org/10.1016/j.str.2010.11.016

@article{874ddb4b587a458a9741deecbfe4bf2a,

title = "The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins",

abstract = "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.",

author = "Harrison, {Oliver J.} and Xiangshu Jin and Soonjin Hong and Fabiana Bahna and Goran Ahlsen and Julia Brasch and Yinghao Wu and Jeremie Vendome and Klara Felsovalyi and Hampton, {Cheri M.} and Troyanovsky, {Regina B.} and Avinoam Ben-Shaul and Joachim Frank and Troyanovsky, {Sergey M.} and Lawrence Shapiro and Barry Honig",

note = "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. ",

year = "2011",

month = feb,

day = "9",

doi = "10.1016/j.str.2010.11.016",

language = "English (US)",

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pages = "244--256",

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Harrison, OJ, Jin, X, Hong, S, Bahna, F, Ahlsen, G, Brasch, J, Wu, Y, Vendome, J, Felsovalyi, K, Hampton, CM, Troyanovsky, RB, Ben-Shaul, A, Frank, J, Troyanovsky, SM, Shapiro, L & Honig, B 2011, 'The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins', Structure, vol. 19, no. 2, pp. 244-256. https://doi.org/10.1016/j.str.2010.11.016

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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The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins

Abstract

Funding

ASJC Scopus subject areas

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Crystal structure of mouse E-cadherin ectodomain

Mouse E-cadherin EC1-2 L175D mutant

Mouse E-cadherin EC1-2 V81D mutant

Cite this

The extracellular architecture of adherens junctions revealed by crystal structures of type i cadherins

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

Crystal structure of mouse E-cadherin ectodomain

Mouse E-cadherin EC1-2 L175D mutant

Mouse E-cadherin EC1-2 V81D mutant

Cite this