title: Dynamic character of human growth hormone and its receptor: normal mode analysis.
abstract: Human growth hormone (hGH) induces dimerization of its binding protein (hGHbp). hGH binds to the first hGHbp (bp1) on site 1, and then the hGH-bp1 heterodimer complex binds to the second hGHbp (bp2) on site 2. Although the interactions of hGH and hGHbps have been studied from different viewpoints, few studies from a dynamic viewpoint have been reported. Especially, since in the SCOP domain database hGHbp is classified as two clear immunoglobulin-like domains, it is of interest to understand how hGH interacts with the hGHbp domains. Therefore, we carried out normal mode analysis (NMA) of free hGH, free bp1, free bp2, and the hGH-bp1 heterodimer complex, as well as the hGH-bp1-bp2 ternary complex to investigate how the dynamics of the proteins change before and after forming the complexes. NMA showed that the domain motion between the N-terminal and the C-terminal domains of free bp1 markedly decreased after binding to hGH, and that the domain motion of bp2 decreased similarly after binding to the hGH-bp1 heterodimer complex. The present study demonstrates that hGH regulates the inter-domain motions of both hGHbps.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Youji
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nojima
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takeda-Shitaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sumikawa
authors.forename: Kenshu
authors.initials: K
authors.lastname: Kamiya
authors.forename: Hideaki
authors.initials: H
authors.lastname: Umeyama
mesh_terms: D019382:Human Growth Hormone / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D011485:Protein Binding / Q000502:physiology; D011986:Receptors, Somatotropin / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone