4OIE

West Nile Virus Non-structural Protein NS1

Summary for 4OIE

• Entry DOI: 10.2210/pdb4oie/pdb
• Related: 4OIG 4OII
• Descriptor: NON-STRUCTURAL PROTEIN NS1, GLYCEROL (3 entities in total)
• Functional Keywords: non-structural protein, flavivirus, west nile virus, ns1, viral protein, structural genomics, center for structural genomics of infectious diseases, csgid
• Biological source: West Nile virus (WNV)
• Cellular location: Virion membrane; Multi-pass membrane protein: U3N977
• Total number of polymer chains: 1
• Total formula weight: 21234.96

Authors

Edeling, M.A.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2014-01-19, release date: 2014-03-05, Last modification date: 2014-04-23)

Primary citation

Edeling, M.A.,Diamond, M.S.,Fremont, D.H.
Structural basis of Flavivirus NS1 assembly and antibody recognition.
Proc.Natl.Acad.Sci.USA, 111:4285-4290, 2014

PubMed Abstract: The Flavivirus nonstructural protein 1 (NS1) is a conserved, membrane-associated and secreted glycoprotein with replication and immune evasion functions. Secreted NS1 is a hexameric, barrel-shaped lipoprotein that can bind back to the plasma membrane of cells. Antibodies targeting cell surface-associated NS1 can be protective in vivo in a manner dependent on Fc effector functions. We describe here the crystal structure of a C-terminal fragment (residues 172-352) of West Nile (WNV) and Dengue virus NS1 proteins at 1.85 and 2.7 Å resolution, respectively. NS1(172-352) assembles as a unique rod-shaped dimer composed of a 16-stranded β-platform flanked on one face by protruding connecting loops. We also determined the 3.0 Å resolution structure of WNV NS1(172-352) with the protective 22NS1 antibody Fab, which engages the loop-face of the rod. The head-to-head NS1(172-352) dimer we observe in crystal lattices is supported by multiangle light and small-angle X-ray scattering studies. We used the available cryo-electron microscopy reconstruction to develop a pseudoatomic model of the NS1 hexamer. The model was constructed with the NS1(172-352) dimeric rod aligned with the long axis of the barrel, and with the loop-face oriented away from the core. Difference densities suggest that the N-terminal region of NS1 forms globular lobes that mediate lateral contacts between dimers in the hexamer. Our model also suggests that the N-terminal lobe forms the surface of the central cavity where lipid binding may occur.

PubMed: 24594604
DOI: 10.1073/pnas.1322036111

Experimental method

X-RAY DIFFRACTION (1.85 Å)