5YZD

Crystal structure of the prefusion form of measles virus fusion protein in complex with a fusion inhibitor peptide (FIP)

Summary for 5YZD

• Entry DOI: 10.2210/pdb5yzd/pdb
• Related: 5YXW 5YZC
• Descriptor: glycoprotein F2, glycoprotein F1,measles virus fusion protein, peptide CBZ-DPN-PHE-GLY, ... (6 entities in total)
• Functional Keywords: glycoprotein, viral protein, fusion protein, paramyxovirus, inhibitor, viral protein-inhibitor complex, viral protein/inhibitor
• Biological source: Measles virus (strain Ichinose-B95a) (MeV); More
• Cellular location: Virion membrane ; Single-pass type I membrane protein : Q786F3
• Total number of polymer chains: 3
• Total formula weight: 56617.81

Authors

Hashiguchi, T.,Fukuda, Y.,Matsuoka, R.,Kuroda, D.,Kubota, M.,Shirogane, Y.,Watanabe, S.,Tsumoto, K.,Kohda, D.,Plemper, R.K.,Yanagi, Y. (deposition date: 2017-12-14, release date: 2018-02-21, Last modification date: 2024-10-16)

Primary citation

Hashiguchi, T.,Fukuda, Y.,Matsuoka, R.,Kuroda, D.,Kubota, M.,Shirogane, Y.,Watanabe, S.,Tsumoto, K.,Kohda, D.,Plemper, R.K.,Yanagi, Y.
Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.
Proc. Natl. Acad. Sci. U.S.A., 115:2496-2501, 2018

PubMed Abstract: Measles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases.

PubMed: 29463726
DOI: 10.1073/pnas.1718957115

Experimental method

X-RAY DIFFRACTION (2.636 Å)