Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain

Usuki, Seigo; Yasutake, Yoshiaki; Tamura, Noriko et al.

Cells, 2020, 9(2), 517

Permalink : https://hdl.handle.net/2115/78370

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アクセス権
open access
URI
https://hdl.handle.net/2115/78370
タイトル
Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain
著者
Usuki, Seigo ; Yasutake, Yoshiaki ; Tamura, Noriko ; Tamura, Tomohiro ; Tanji, Kunikazu ; Saitoh, Takashi ; Murai, Yuta ; Mikami, Daisuke ; Yuyama, Kohei ; Monde, Kenji ; Mukai, Katsuyuki ; Igarashi, Yasuyuki
著者名
Usuki, Seigo
著者名
Yasutake, Yoshiaki
著者名
Tamura, Noriko
著者名
Tamura, Tomohiro
著者名
Tanji, Kunikazu
著者名
Saitoh, Takashi
著者名
Murai, Yuta
著者名
Mikami, Daisuke
著者名
Yuyama, Kohei
著者名
Monde, Kenji
著者名
Mukai, Katsuyuki
e-Rad_Researcher
70091965
著者名
Igarashi, Yasuyuki
言語
英語
キーワード
ceramide
konjac
semaphorin3A
neurite outgrowth
neuropilin 1
endoglycoceramidase
sphingadienine
発行日
2020-02
出版者
MDPI
収録物名
Cells
巻(号)
9(2)
ページ
517
抄録
Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and alpha-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mu M dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand-receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 4.0 International
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3390/cells9020517