The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors

Thomas P.J. Garrett; Neil M. McKern; Meizhen Lou; Thomas C. Elleman; Timothy E. Adams; George O. Lovrecz; Michael Kofler; Robert N. Jorissen; Edouard C. Nice; Antony W. Burgess; Colin W. Ward

doi:10.1016/S1097-2765(03)00048-0

The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors

Thomas P.J. Garrett, Neil M. McKern, Meizhen Lou, Thomas C. Elleman, Timothy E. Adams, George O. Lovrecz, Michael Kofler, Robert N. Jorissen, Edouard C. Nice, Antony W. Burgess, Colin W. Ward

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511 Citations (Scopus)

Abstract

ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 Å resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.

Original language	English
Pages (from-to)	495-505
Number of pages	11
Journal	Molecular Cell
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/S1097-2765(03)00048-0
Publication status	Published or Issued - 1 Feb 2003
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(03)00048-0

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Garrett, T. P. J., McKern, N. M., Lou, M., Elleman, T. C., Adams, T. E., Lovrecz, G. O., Kofler, M., Jorissen, R. N., Nice, E. C., Burgess, A. W., & Ward, C. W. (2003). The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Molecular Cell, 11(2), 495-505. https://doi.org/10.1016/S1097-2765(03)00048-0

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title = "The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors",

abstract = "ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 {\AA} resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.",

author = "Garrett, {Thomas P.J.} and McKern, {Neil M.} and Meizhen Lou and Elleman, {Thomas C.} and Adams, {Timothy E.} and Lovrecz, {George O.} and Michael Kofler and Jorissen, {Robert N.} and Nice, {Edouard C.} and Burgess, {Antony W.} and Ward, {Colin W.}",

note = "Funding Information: We thank Drs. Mark Lemmon and Kathryn Ferguson for sharing information prior to publication and Dr. Louis Lu, Dr. Nathan Hall, Mr. Albert van Donkelaar, Ms. Julie Rothaker, Ms. Kim Richards, and Ms. Jenny Lewis for valuable contributions. This work was supported in part by the Australian and Victorian Governments through CSIRO, the CRC program, and the Biomolecular Research Institute and by grants to A.W.B. and E.C.N. from the NH&MRC of Australia.",

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AU - Lovrecz, George O.

AU - Kofler, Michael

AU - Jorissen, Robert N.

AU - Nice, Edouard C.

AU - Burgess, Antony W.

AU - Ward, Colin W.

N1 - Funding Information: We thank Drs. Mark Lemmon and Kathryn Ferguson for sharing information prior to publication and Dr. Louis Lu, Dr. Nathan Hall, Mr. Albert van Donkelaar, Ms. Julie Rothaker, Ms. Kim Richards, and Ms. Jenny Lewis for valuable contributions. This work was supported in part by the Australian and Victorian Governments through CSIRO, the CRC program, and the Biomolecular Research Institute and by grants to A.W.B. and E.C.N. from the NH&MRC of Australia.

PY - 2003/2/1

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N2 - ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 Å resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.

AB - ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 Å resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.

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The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors

Abstract

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