Crystal structure of Caenorhabditis elegans HER-1 and characterization of the interaction between HER-1 and TRA-2A.
HER-1 is a secreted protein that promotes male development in the nematode Caenorhabditis elegans. HER-1 inhibits the function of TRA-2A, a multipass integral membrane protein thought to serve as its receptor. We report here the 1.5-A crystal structure of HER-1. The structure was solved by the multiwavelength anomalous diffraction method by using selenomethionyl-substituted HER-1 produced in Chinese hamster ovary cells. The HER-1 structure consists of two all-helical domains and is not closely homologous to any known structure. Sites of amino acid substitutions known to impair HER-1 function were mapped on the HER-1 structure and classified according to the likely mechanism by which they affect HER-1 activity. A subset of these and other amino acid substitutions on the HER-1 surface were assayed for their ability to disrupt interactions between HER-1 and TRA-2A-expressing cells, and a localized region on the HER-1 surface important for mediating this interaction was identified.
Department of Biophysics and Biophysical Chemistry and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Brent Y
BY
Hamaoka
Charles E
CE
Dann
Brian V
BV
Geisbrecht
Daniel J
DJ
Leahy
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012645:Selenomethionine; D014961:X-Ray Diffraction
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C079744:her-1 protein, C elegans; C076107:tra-2 protein, C elegans; D012645:Selenomethionine