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 A 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.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, 3050, Parkville, Victoria, Australia. tgarrett@wehi.edu.au
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Garrett
authors.forename: Neil M
authors.initials: NM
authors.lastname: McKern
authors.forename: Meizhen
authors.initials: M
authors.lastname: Lou
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Elleman
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Adams
authors.forename: George O
authors.initials: GO
authors.lastname: Lovrecz
authors.forename: Michael
authors.initials: M
authors.lastname: Kofler
authors.forename: Robert N
authors.initials: RN
authors.lastname: Jorissen
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
authors.forename: Colin W
authors.initials: CW
authors.lastname: Ward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000235:genetics; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D018076:DNA, Complementary; D066246:ErbB Receptors; D008024:Ligands; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011994:Recombinant Proteins