PDBsum entry 3m1b

Immune system/inhibitor

PDB id: 3m1b

Contents

Protein chains

263 a.a. *

99 a.a. *

11 a.a. *

12 a.a. *

* Residue conservation analysis

PDB id:

3m1b

Name:

Immune system/inhibitor

Title:

Crystal structure of human fcrn with a dimeric peptide inhibitor

Structure:

Igg receptor fcrn large subunit p51. Chain: a, c, e, g. Fragment: unp residues 24-290. Synonym: fcrn, neonatal fc receptor, igg fc fragment receptor transporter alpha chain. Engineered: yes. Beta-2-microglobulin. Chain: b, d, f, h. Fragment: unp residues 21-119.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fcgrt, fcrn. Expressed in: cricetinae. Expression_system_taxid: 10026. Expression_system_cell: chok1sv cells. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes

Resolution:

3.10Å R-factor: 0.318 R-free: 0.397

Authors:

A.R.Mezo,V.Sridhar,J.Badger,P.Sakorafas,V.Nienaber

Key ref:

A.R.Mezo et al. (2010). X-ray crystal structures of monomeric and dimeric peptide inhibitors in complex with the human neonatal Fc receptor, FcRn. J Biol Chem, 285, 27694-27701. PubMed id: 20592032

Date:

04-Mar-10 Release date: 16-Jun-10

Protein chains

P55899  (FCGRN_HUMAN) -  IgG receptor FcRn large subunit p51 from Homo sapiens

Seq: 365 a.a.

Struc: 263 a.a.

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

Protein chain

No UniProt id for this chain

Struc: 11 a.a.

Protein chain

No UniProt id for this chain

Struc: 12 a.a.

J Biol Chem 285:27694-27701 (2010)

PubMed id: 20592032

X-ray crystal structures of monomeric and dimeric peptide inhibitors in complex with the human neonatal Fc receptor, FcRn.

A.R.Mezo, V.Sridhar, J.Badger, P.Sakorafas, V.Nienaber.

ABSTRACT

The neonatal Fc receptor, FcRn, is responsible for the long half-life of IgG molecules in vivo and is a potential therapeutic target for the treatment of autoimmune diseases. A family of peptides comprising the consensus motif GHFGGXY, where X is preferably a hydrophobic amino acid, was shown previously to inhibit the human IgG:human FcRn protein-protein interaction [Proc. Nat. Acad. Sci. USA, 2008, 105, 2337-2342]. Herein, the X-ray crystal structure of a representative monomeric peptide in complex with human FcRn was solved to 2.6 A resolution. The structure shows that the peptide binds to human FcRn at the same general binding site as does the Fc domain of IgG. The data correlate well with structure-activity relationship data relating to how the peptide family binds to human FcRn. In addition, the X-ray crystal structure of a representative dimeric peptide in complex with human FcRn shows how the bivalent ligand can bridge two FcRn molecules which may be relevant to the mechanism by which the dimeric peptides inhibit FcRn and increase IgG catabolism in vivo. Modeling of the peptide:FcRn structure as compared to available structural data on Fc and FcRn suggest that the His6 and Phe7 (peptide) partially mimic the interaction of His310 and Ile253 (Fc) in binding to FcRn, but using a different backbone topology.