Multimer formation is indispensable to the intrinsicbiologicalfunctions of many natural proteins. For example， the human immunoglobulin G (IgG) antibody has two variable regions (heavy chain variable domain [VH] and light chain variable domain [VL]) that must be assembled for specific antigen binding， and homodimerization of the antibody's Fc domain is essential for eliciting therapeutic effector functions. For the more efficient high-throughput directed evolution of multimeric proteins with ease of cultivation and handling， here we report a membrane protein drift and assembly (MPDA) system， in which a multimeric protein is displayed on a bacterial inner membrane by drifting and auto-assembling membrane-anchored subunit polypeptides. This system enabled the auto-assembly of membrane-tethered Fv domains (VH and VL) or the monomeric Fc domain into a functional hetero- or homodimeric protein complex on the bacterial inner membrane. This system could also be used to enrich a desired engineered Fc variant from a mixture containing a million-fold excess of wild-type Fc domain， indicating the applicability of the MPDA system for the high-throughput directed evolution of a variety of multimeric proteins， such as cytokines， enzymes， or structural proteins.