Human FcRL5 is an Fc receptor that simultaneously engages two IgGs.

ABSTRACT: The Fc receptors play crucial roles in initiating the effector functions of immunoglobulins. FcRL5 is a prominent target in B cell malignancies and has been implicated as a receptor for immunoglobulin G (IgG). However, the molecular mechanism remained unclear. Here, we demonstrate that human FcRL5, but not its mouse counterpart, is a bona fide IgG-Fc (Fcγ) receptor that uniquely requires the presence of two Fcγ molecules in close proximity to form a robust interaction. Cryo-electron microscopy reveals that FcRL5 optimally engages two Fcγ molecules positioned at a 60° angle, with its D1-D2 domains binding to the first Fcγ molecule, while its D3 domain arches over the second Fcγ. This distinctive binding capability enables FcRL5 to specifically recognize IgG immune complexes (ICs), with the

SUBMITTER: Chen S 

PROVIDER: S-EPMC12757038 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature