Dimerization of the Extracellular Domain of the Human Growth Hormone Receptor by a Single Hormone Molecule

American Association for the Advancement of Science (AAAS) - Tập 254 Số 5033 - Trang 821-825 - 1991
Brian C. Cunningham1, Mark Ultsch1, Abraham M. de Vos1, Michael G. Mulkerrin1, Karl R. Clauser1, James A. Wells1
1Departments of Protein Engineering, Medicinal and Analytical Chemistry, and Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.

Tóm tắt

Human growth hormone (hGH) forms a 1:2 complex with the extracellular domain of its receptor-binding protein (hGHbp) as studied by crystallization, size exclusion chromatography, calorimetry, and a previously undescribed fluorescence quenching assay. These and other experiments with protein engineered variants of hGH have led to the identification of the binding determinants for two distinct but adjacent sites on hGH for the hGHbp, and the data indicated that there are two overlapping binding sites on the hGHbp for hGH. Furthermore, the binding of hGH to the hGHbp occurred sequentially; a first hGHbp molecule bound to site 1 on hGH and then a second hGHbp bound to site 2. Hormone-induced receptor dimerization is proposed to be relevant to the signal transduction mechanism for the hGH receptor and other related cytokine receptors.

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Tài liệu tham khảo

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American Association for the Advancement of Science (AAAS)

Tập 254 Số 5033

821-825

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