The 1.51-Angstrom structure of the poxvirus L1 protein, a target of potent neutralizing antibodies.
Although eradicated from nature more than two decades ago, the threat of smallpox has reemerged because of concerns over its use as a biological weapon. We present the structure of the poxvirus L1 protein, a molecule that is conserved throughout the poxvirus family and is nearly identical in vaccinia virus and in variola virus, which causes smallpox. L1 is a myristoylated envelope protein that is a potent target for neutralizing antibodies and an important component of current experimental vaccines. The L1 structure reveals a hydrophobic cavity located adjacent to its N terminus. The cavity would be capable of shielding the myristate moiety, which is essential for virion assembly. The structure of L1 is a step in the elucidation of molecular mechanisms common to all poxviruses that may stimulate the design of safer vaccines and new antipoxvirus drugs.
Su
Hua-Poo
HP
Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Garman
Scott C
SC
Allison
Timothy J
TJ
Fogg
Christiana
C
Moss
Bernard
B
Garboczi
David N
DN
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009227:Myristic Acids / Q000737:chemistry; D009500:Neutralization Tests; D011212:Poxviridae / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012900:Smallpox Vaccine / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D055672:Static Electricity; D014616:Vaccinia virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012901:Variola virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D004220:Disulfides; C109350:I1 protein, vaccinia virus; D009227:Myristic Acids; D012900:Smallpox Vaccine; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins