4N0F

Human FcRn complexed with human serum albumin

Summary for 4N0F

• Entry DOI: 10.2210/pdb4n0f/pdb
• Related: 1AO6 1EXU 4N0U
• Descriptor: IgG receptor FcRn large subunit p51, Beta-2-microglobulin, Serum albumin (3 entities in total)
• Functional Keywords: alpha/beta, receptor, igg constant domain, membrane, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein (By similarity): P55899; Secreted: P61769 P02768
• Total number of polymer chains: 12
• Total formula weight: 433760.87

Authors

Oganesyan, V.,Wu, H.,Dall'Acqua, W.F. (deposition date: 2013-10-01, release date: 2014-02-05, Last modification date: 2024-10-16)

Primary citation

Oganesyan, V.,Damschroder, M.M.,Cook, K.E.,Li, Q.,Gao, C.,Wu, H.,Dall'acqua, W.F.
Structural Insights into Neonatal Fc Receptor-based Recycling Mechanisms.
J.Biol.Chem., 289:7812-7824, 2014

PubMed Abstract: We report the three-dimensional structure of human neonatal Fc receptor (FcRn) bound concurrently to its two known ligands. More particularly, we solved the crystal structure of the complex between human FcRn, wild-type human serum albumin (HSA), and a human Fc engineered for improved pharmacokinetics properties (Fc-YTE). The crystal structure of human FcRn bound to wild-type HSA alone is also presented. HSA domain III exhibits an extensive interface of contact with FcRn, whereas domain I plays a lesser role. A molecular explanation for the HSA recycling mechanism is provided with the identification of FcRn His(161) as the only potential direct contributor to the corresponding pH-dependent process. At last, this study also allows an accurate structural definition of residues considered for decades as important to the human IgG/FcRn interaction and reveals Fc His(310) as a significant contributor to pH-dependent binding. Finally, we explain various structural mechanisms by which several Fc mutations (including YTE) result in increased human IgG binding to FcRn. Our study provides an unprecedented relevant understanding of the molecular basis of human Fc interaction with human FcRn.

PubMed: 24469444
DOI: 10.1074/jbc.M113.537563

Experimental method

X-RAY DIFFRACTION (3.02 Å)