4OIG

Dengue Virus Non-structural Protein NS1

Summary for 4OIG

• Entry DOI: 10.2210/pdb4oig/pdb
• Related: 4OIE 4OII
• Descriptor: Non-structural protein 1, NS1, SULFATE ION (3 entities in total)
• Functional Keywords: dengue virus, non-structural protein, ns1, flavivirus viral protein, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein
• Biological source: Dengue virus 1 (DENV-1)
• Cellular location: Capsid protein C: Virion. Peptide pr: Secreted . Small envelope protein M: Virion membrane ; Multi-pass membrane protein . Envelope protein E: Virion membrane ; Multi-pass membrane protein . Non-structural protein 1: Secreted . Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P17763
• Total number of polymer chains: 4
• Total formula weight: 86790.26

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: 2024-11-20)

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 (2.69 Å)