Conformational change of the crystal structure of TN1-Fab fragment with and without binding of human thrombopoietin.

Arai, Shigeki; Tamada, Taro; Maeda, Yoshitake*; Kuroki, Ryota

The mouse antibody TN1 recognizes the human thrombopoietin (hTPO) that primarily stimulates megakaryocytopoiesis and platelet production. In order to clarify the mechanism of the neutralizing activity of the TN1 antibody, the crystal structure of TN1-Fab was determined to 2.1 resolution and was compared with that of TN1-Fab / hTPO complex (PDB id 1V7M and 1V7N). It was found that only side chain level "Induced-fit" upon the antigen binding was enough for TN1 to recognize hTPO. On the other hand, the relative angle of the variable- and constant-regions of the hTPO unbound form of TN1-Fab was slightly shifted from those of TN1-Fab / hTPO complex (rms deviation = 2.4 for all C atoms of Fab). In this presentation, we will explain the details of the conformational change of the crystal structure of TN1-Fab fragment with and without binding of hTPO.