Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN.
Dengue virus (DENV) is a significant human pathogen that causes millions of infections and results in about 24,000 deaths each year. Dendritic cell-specific ICAM3 grabbing nonintegrin (DC-SIGN), abundant in immature dendritic cells, was previously reported as being an ancillary receptor interacting with the surface of DENV. The structure of DENV in complex with the carbohydrate recognition domain (CRD) of DC-SIGN was determined by cryo-electron microscopy at 25 A resolution. One CRD monomer was found to bind to two glycosylation sites at Asn67 of two neighboring glycoproteins in each icosahedral asymmetric unit, leaving the third Asn67 residue vacant. The vacancy at the third Asn67 site is a result of the nonequivalence of the glycoprotein environments, leaving space for the primary receptor binding to domain III of E. The use of carbohydrate moieties for receptor binding sites suggests a mechanism for avoiding immune surveillance.
Department of Biological Sciences, Lilly Hall, 915 W. State Street, Purdue University, West Lafayette, IN 47907, USA.
Elena
E
Pokidysheva
Ying
Y
Zhang
Anthony J
AJ
Battisti
Carol M
CM
Bator-Kelly
Paul R
PR
Chipman
Chuan
C
Xiao
G Glenn
GG
Gregorio
Wayne A
WA
Hendrickson
Richard J
RJ
Kuhn
Michael G
MG
Rossmann
D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D003713:Dendritic Cells / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry* / Q000472:pathogenicity / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D037181:Lectins, C-Type / Q000737:chemistry*; D008958:Models, Molecular; D046912:Multiprotein Complexes; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry*; D011991:Receptors, Virus / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin