Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae

Article

Vizarraga, David / Kawamoto, Akihiro / Matsumoto, U. / Illanes, Ramiro / Perez-Luque, Rosa / Martín, Jesus / Mazzolini, Rocco / Bierge, Paula / Pich, Oscar Q. / Espasa, Mateu / Sanfeliu, Isabel / Esperalba, Juliana / Fernandez-Huerta, Miguel / Scheffer, Margot P. / Pinyol, Jaume / Frangakis, Achilleas S. / Lluch-Senar, Maria / Mori, Shigetarou / Shibayama, Keigo / Kenri, Tsuyoshi / Kato, Takayuki / Namba, Keiichi / Fita, Ignacio / Miyata, Makoto / Aparicio, David

/ 川本, 晃大 / 松本, 優 / / / / / / / / / / / / / / / 森, 茂太郎 / 柴山, 恵吾 / 見理, 剛 / 加藤, 貴之 / 難波, 啓一 / / 宮田, 真人 /

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研究チームは、ヒトに肺炎を発症させる細菌、マイコプラズマ・ニューモニエがヒトに感染するために接着と滑走を行うためのタンパク質複合体、"Nap"の構造を、世界で初めて原子レベルで明らかにしました。

Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae, and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections.

This work was supported by grants BFU2018-101265-B-100 (MINECO) to I.F., BIO2017-84166-R (MINECO) to J.P., and BES-2015-076104 (MINECO) to M.L.S., JSPS KAKENHI Grant Number JP25000013 to K.N., and a FEDER project from Instituto de Salud Carlos III (ISCIII, Accion Estrategica en Salud 2016). This work was supported by a Grant-in-Aid for Scientific Research on the Innovative Area "Harmonized Supramolecular Motility Machinery and Its Diversity" (MEXT KAKENH, JP24117002 to M.M., JP25117530 and JP15H01337 to T.K.), Grants-in-Aid for Scientific Research (B) and (A) (MEXT KAKENHI, JP24390107, JP17H01544), JST CREST (JPMJCR19S5), Osaka City University (OCU) Strategic Research Grant 2018 for top priority researches to M.M. D.A. acknowledges a María de Maeztu Unit of Excellence grant MDM-2014-0435.

eng

5188

マイコプラズマ・ニューモニエ / 電子顕微鏡

Electron microscopy / Immunology / Microbiology / Structural biology / X-ray crystallography

publisher

Instituto de Biologia Molecular de Barcelona / Osaka University / Osaka City University / Instituto de Biologia Molecular de Barcelona / Instituto de Biologia Molecular de Barcelona / Instituto de Biologia Molecular de Barcelona / The Barcelona Institute of Science and Technology / Universitat Autonoma de Barcelona / Universitat Autonoma de Barcelona / Universitat Autonoma de Barcelona / Universitat Autonoma de Barcelona / Universitat Autonoma de Barcelona / Universitat Autonoma de Barcelona / Buchmann Institute for Molecular Life Sciences / Universitat Autonoma de Barcelona / Buchmann Institute for Molecular Life Sciences / The Barcelona Institute of Science and Technology / National Institute of Infectious Diseases / National Institute of Infectious Diseases / National Institute of Infectious Diseases / Osaka University / Osaka University, RIKEN Center for Biosystems Dynamics Research and SPring-8 Center / Instituto de Biologia Molecular de Barcelona / Osaka City University / Instituto de Biologia Molecular de Barcelona

2020-10-14

Nature

2041-1723

AA12645905

Journal Article

https://doi.org/10.1038/s41467-020-18777-y

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