A novel neuropilin-1-binding sequence in the human T-cell lymphotropic virus type 1 envelope glycoprotein

Hideki Kusunoki; Toshiyuki Tanaka; Toshiyuki Kohno; Kazuhiko Matsuhashi; Kazuo Hosoda; Kaori Wakamatsu; Isao Hamaguchi

doi:10.1016/j.bbapap.2018.02.003

A novel neuropilin-1-binding sequence in the human T-cell lymphotropic virus type 1 envelope glycoprotein

Biochim Biophys Acta Proteins Proteom. 2018 Apr;1866(4):541-548. doi: 10.1016/j.bbapap.2018.02.003. Epub 2018 Feb 16.

Authors

Hideki Kusunoki¹, Toshiyuki Tanaka², Toshiyuki Kohno³, Kazuhiko Matsuhashi⁴, Kazuo Hosoda⁵, Kaori Wakamatsu⁵, Isao Hamaguchi⁶

Affiliations

¹ Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address: kusunoki@niid.go.jp.
² Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
³ Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
⁴ Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan; Department of Pediatrics, The Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
⁵ Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
⁶ Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address: 130hama@niid.go.jp.

PMID: 29458191
DOI: 10.1016/j.bbapap.2018.02.003

Abstract

Entry of human T-cell lymphotropic virus type 1 (HTLV-1) into host cells is mainly mediated by interactions between the viral envelope glycoprotein surface unit (SU) and three host receptors: glucose transporter type 1, heparin/heparan sulfate proteoglycan, and neuropilin-1 (Nrp1). Here, we analyzed the interaction between HTLV-1 SU and Nrp1 using nuclear magnetic resonance and isothermal titration calorimetry. We found that two SU peptides, residues 85-94 and residues 304-312, bound directly to the Nrp1 b1 domain with affinities of 7.4 and 17.7 μM, respectively. The binding modes of both peptides were almost identical to those observed for Tuftsin and vascular endothelial growth factor A binding to the Nrp1 b1 domain. These results suggest that the C-terminal region of HTLV-1 SU contains a novel site for direct binding of virus to the Nrp1 b1 domain. Our biophysical characterization of the SU peptides may help in developing inhibitors of HTLV-1 entry.

Keywords: C-end rule/CendR; HTLV-1; NMR; Neuropilin-1; Surface unit/SU.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Gene Products, env / chemistry*
Gene Products, env / genetics
Gene Products, env / metabolism
Human T-lymphotropic virus 1 / chemistry*
Human T-lymphotropic virus 1 / genetics
Human T-lymphotropic virus 1 / metabolism
Humans
Neuropilin-1 / chemistry*
Neuropilin-1 / genetics
Neuropilin-1 / metabolism
Protein Binding
Retroviridae Proteins, Oncogenic / chemistry*
Retroviridae Proteins, Oncogenic / genetics
Retroviridae Proteins, Oncogenic / metabolism

Substances

Gene Products, env
Retroviridae Proteins, Oncogenic
gp46 protein, Human T-cell leukemia virus type I
Neuropilin-1