Generation of self-clusters of galectin-1 in the farnesyl-bound form.
Ras protein is involved in a signal transduction cascade in cell growth, and cluster formation of H-Ras and human galectin-1 (Gal-1) complex is considered to be crucial to achieve its physiological roles. It is considered that the complex is formed through interactions between Gal-1 and the farnesyl group (farnesyl-dependent model), post-translationally modified to the C-terminal Cys, of H-Ras. We investigated the role of farnesyl-bound Gal-1 in the cluster formation by analyzing the structure and properties of Gal-1 bound to farnesyl thiosalicylic acid (FTS), a competitive inhibitor of the binding of H-Ras to Gal-1. Gal-1 exhibited self-cluster formation upon interaction with FTS, and small- and large-size clusters were formed depending on FTS concentration. The galactoside-binding pocket of Gal-1 in the FTS-bound form was found to play an important role in small-size cluster formation. Large-size clusters were likely formed by the interaction among the hydrophobic sites of Gal-1 in the FTS-bound form. The present results indicate that Gal-1 in the FTS-bound form has the ability to form self-clusters as well as intrinsic lectin activity. Relevance of the self-clustering of FTS-bound Gal-1 to the cluster formation of the H-Ras-Gal-1complex was discussed by taking account of the farnesyl-dependent model and another (Raf-dependent) model.
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Kazumi
K
Yamaguchi
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Yusuke
Y
Niwa
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Takakazu
T
Nakabayashi
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Hirotsugu
H
Hiramatsu
D001665:Binding Sites; D005204:Farnesol / Q000031:analogs & derivatives* / Q000378:metabolism; D037483:Galectin 1 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism*
D037483:Galectin 1; C445499:LGALS1 protein, human; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)