Structure and intracellular targeting of the SARS-coronavirus Orf7a accessory protein.
The open reading frame (ORF) 7a of the SARS-associated coronavirus (SARS-CoV) encodes a unique type I transmembrane protein of unknown function. We have determined the 1.8 A resolution crystal structure of the N-terminal ectodomain of orf7a, revealing a compact seven-stranded beta sandwich unexpectedly similar in fold and topology to members of the Ig superfamily. We also demonstrate that, in SARS-CoV- infected cells, the orf7a protein is expressed and retained intracellularly. Confocal microscopy studies using orf7a and orf7a/CD4 chimeras implicate the short cytoplasmic tail and transmembrane domain in trafficking of the protein within the endoplasmic reticulum and Golgi network. Taken together, our findings provide a structural and cellular framework in which to explore the role of orf7a in SARS-CoV pathogenesis.
Nelson
Christopher A
CA
Department of Pathology and Immunology, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Pekosz
Andrew
A
Lee
Chung A
CA
Diamond
Michael S
MS
Fremont
Daved H
DH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008958:Models, Molecular; D016366:Open Reading Frames; D011233:Precipitin Tests; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; C515314:ORF7b protein, SARS coronavirus; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins