DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.
DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.
Tabarani
Georges
G
Laboratoire des Protéines Membranaires, France.
Thépaut
Michel
M
Stroebel
David
D
Ebel
Christine
C
Vivès
Corinne
C
Vachette
Patrice
P
Durand
Dominique
D
Fieschi
Franck
F
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002942:Circular Dichroism; D003001:Cloning, Molecular; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000737:chemistry / Q000502:physiology*; D008024:Ligands; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation; D014965:X-Rays; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin