caa a22 4500 475744209 CHVBK 20180406123508.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1023/A:1007059820834 doi (NATIONALLICENCE)springer-10.1023/A:1007059820834 Molecular Modeling of Human Serum Transferrin for Rationalizing the Changes in Its Physicochemical Properties Induced by Iron Binding. Implication of the Mechanism of Binding to Its Receptor [Elektronische Daten] [Hirofumi Yajima, Tetsuya Sakajiri, Takeshi Kikuchi, Masahiko Morita, Tadahiro Ishii] In order to rationalize the physicochemical properties of human serum-transferrin (STf) and the STf-receptor (TfR) recognition process, we have tried to predict the 3D structures of apo- and iron-loaded STf using a homology modeling technique to study the changes in the structural characteristics that take place upon the uptake of iron by STf in solution. The crystal structures of both forms for ovotransferrin were used as templates for the STf modeling. The modeled structure of STf gave a satisfactory interpretation for the typical physicochemical properties such that (1) STf has a negative electrophoretic mobility and its value increases with iron uptake, and (2) the radius of gyration Rg of Tf decreases with iron uptake. It was found that upon iron binding, interdomain closures take place with large movements of the NII and CII subdomains comprising the N- and C-lobes in STf through a hinge-bending motion, accompanied by the opening of the bridge region with a displacement of more than 15 Å. Moreover, in view of the findings from our capillary electrophoresis experiments that the electrostatic interactions significantly contribute to a specific binding of Fe2-STf with TfR, it is inferred that the connecting (bridge) and its neighboring region associated with a surface exposure of negative charge play an important role in the STf-receptor recognition process. Plenum Publishing Corporation, 2000 Serum transferrin nationallicence modeling nationallicence accessible surface area nationallicence surface charge nationallicence molecular recognition nationallicence Yajima Hirofumi Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut Sakajiri Tetsuya Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut Kikuchi Takeshi Frontier Research Center for Computational Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, 278-8510, Chiba, Japan aut Morita Masahiko Department of Applied Mathematics, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut Ishii Tadahiro Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/3(2000-04-01), 215-223 0277-8033 19:3<215 2000 19 10930 https://doi.org/10.1023/A:1007059820834 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007059820834 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yajima Hirofumi Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut NATIONALLICENCE 700 1- Sakajiri Tetsuya Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut NATIONALLICENCE 700 1- Kikuchi Takeshi Frontier Research Center for Computational Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, 278-8510, Chiba, Japan aut NATIONALLICENCE 700 1- Morita Masahiko Department of Applied Mathematics, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut NATIONALLICENCE 700 1- Ishii Tadahiro Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, 162-8601, Tokyo, Japan aut NATIONALLICENCE 773 0- Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/3(2000-04-01), 215-223 0277-8033 19:3<215 2000 19 10930 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer