Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR

Science. 2001 Dec 7;294(5549):2163-6. doi: 10.1126/science.1066371.

Abstract

Dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism
  • Calcium / metabolism
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules*
  • Collectins
  • Crystallization
  • Crystallography, X-Ray
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / metabolism
  • Humans
  • Hydrogen Bonding
  • Lectins / chemistry*
  • Lectins / metabolism*
  • Lectins, C-Type*
  • Ligands
  • Mannose / chemistry
  • Mannose / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism*
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism*

Substances

  • CLEC4M protein, human
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Collectins
  • DC-specific ICAM-3 grabbing nonintegrin
  • Glycoproteins
  • HIV Envelope Protein gp120
  • Lectins
  • Lectins, C-Type
  • Ligands
  • Oligosaccharides
  • Receptors, Cell Surface
  • Mannose
  • Calcium
  • Acetylglucosamine

Associated data

  • PDB/1K9I
  • PDB/1K9J