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Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain
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| Title: | Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain |
| Authors: | Usuki, Seigo Browse this author | | Yasutake, Yoshiaki Browse this author | | Tamura, Noriko Browse this author | | Tamura, Tomohiro Browse this author | | Tanji, Kunikazu Browse this author | | Saitoh, Takashi Browse this author | | Murai, Yuta Browse this author | | Mikami, Daisuke Browse this author | | Yuyama, Kohei Browse this author | | Monde, Kenji Browse this author | | Mukai, Katsuyuki Browse this author | | Igarashi, Yasuyuki Browse this author →KAKEN DB |
| Keywords: | ceramide | | konjac | | semaphorin3A | | neurite outgrowth | | neuropilin 1 | | endoglycoceramidase | | sphingadienine |
| Issue Date: | Feb-2020 |
| Publisher: | MDPI |
| Journal Title: | Cells |
| Volume: | 9 |
| Issue: | 2 |
| Start Page: | 517 |
| Publisher DOI: | 10.3390/cells9020517 |
| Abstract: | 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. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/78370 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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