Figure 6

Structure of FcRL5, Fc/FcRL5 and glycosylated Fc domain determined from homology modeling and MD simulations.

(a) Shown is the structure of the FcRL5 model near the end of equilibration simulations, showing well formed secondary and tertiary structures that are expected from the crystal structure of FcγRI, which was used as the initial template. (b) Overview of the structure of the Fc/FcRL5 complex, with the Fc colored red and cyan and the FcRL5 colored as in (a). The known structure of Fc/FcγRIII was used to initially position FcRL5 in contact with the Fc domain. (c) Detailed view of the contact region of the Fc/FcRL5 complex. The Fc residues that are frequently within 3Å of FcRL5 near the end of the equilibration simulation are shown to give a sense of the number and scope of contact region. Although these proteins remained in contact for the duration of the simulations, the contact was weaker than that in the Fc/FcγRIII complex (Figure S10). (d) The upper panel is the initial structure of the glycosylated Fc domain, where the atoms of the complex are depicted as van der Waals spheres. Shown in blue is the hFc, while the colors for the sugars are as depicted in the schematic of the Man₅GlcNAc₂ glycan shown on the left, where mannose residues are circles, the N-acetylglucosamines are squares and the asparagine residue is an oval. Two views of the complex, differing by 90° rotation about the long axis, are shown. The lower panel shows the monomer after ~125 ns. In this, one glycan chain remains closely associated with the C_γ2 domain and remains buried within the cavity. However, the other chain has adopted a structure that interacts with the C_γ2 domain only via the di-N-acetylchitobiose core. In this more loosely bound configuration, the α1–6 mannose branch residues of the glycan (circled in the schematic) are near to the cavity entrance and therefore more accessible to potential interactions with lectins such as DC-SIGN.