An extended conformation of the macrophage mannose receptor

The macrophage mannose receptor mediates phagocytosis of pathogenic microor ganisms and endocytosis of potentially harmful soluble glycoproteins by rec ognition of their defining carbohydrate structures. The mannose receptor is the prototype for a family of receptors each having an extracellular regio n consisting of 8-10 domains related to C-type carbohydrate recognition dom ains (CRDs), a fibronectin type II repeat and an N-terminal cysteine-rich d omain. Hydrodynamic analysis and proteolysis experiments performed on fragm ents of the extracellular region of the receptor have been used to investig ate its conformation. Size and shape parameters derived from sedimentation and diffusion coefficients indicate that the receptor is a monomeric, elong ated and asymmetric molecule. Proteolysis experiments indicate the presence of close contacts between several pairs of domains and exposed linker regi ons separating CRDs 3 and 6 from their neighboring domains. Hydrodynamic co efficients predicted for modeled receptor conformations are consistent with an extended conformation with close contacts between three pairs of CRDs, The N-terminal cysteine rich domain and the fibronectin type II repeat appe ar to increase the rigidity of the molecule. The rigid, extended conformati on of the receptor places domains with different functions at distinct posi tions with respect to the membrane.