OLIGOMERIC STATE OF ERBB-FAMILY EXTRACELLULAR DOMAIN +/- ANTIBODY FRAGMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epidermal growth factor receptor (EGFR, erbB1) and homologues are suspected of a dimerized signaling state, but only EGFR-ecd has been seen as a dimer by single crystal x-ray diffraction. In fact, over-expressed erbB2 (HER2) is oncogenic, but no HER2-ecd dimers are seen even in concentrated solution. Thus, we are surprised to see HER2 trimers in crystals of HER2-ecd/Fab37 complex. We suspect these trimers require ~1 M phosphate and Fab37, but the question about whether trimers exist in solution or only upon crystal formation is an open one. The answer will guide thinking about the relevance of our trimers to presumed high-oligomeric states in membrane microdomains.