3S9M

Complex between transferrin receptor 1 and transferrin with iron in the N-Lobe, cryocooled 1

Summary for 3S9M

• Entry DOI: 10.2210/pdb3s9m/pdb
• Related: 1A8E 1CX8 2HAU 3S9L 3S9N
• Descriptor: Transferrin receptor protein 1, Serotransferrin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: transferrin receptor complex, transferrin superfamily, carboxypeptidase like, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 301781.33

Authors

Eckenroth, B.E.,Steere, A.N.,Mason, A.B.,Everse, S.J. (deposition date: 2011-06-01, release date: 2011-08-10, Last modification date: 2024-11-06)

Primary citation

Eckenroth, B.E.,Steere, A.N.,Chasteen, N.D.,Everse, S.J.,Mason, A.B.
How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH.
Proc.Natl.Acad.Sci.USA, 108:13089-13094, 2011

PubMed Abstract: Delivery of iron to cells requires binding of two iron-containing human transferrin (hTF) molecules to the specific homodimeric transferrin receptor (TFR) on the cell surface. Through receptor-mediated endocytosis involving lower pH, salt, and an unidentified chelator, iron is rapidly released from hTF within the endosome. The crystal structure of a monoferric N-lobe hTF/TFR complex (3.22-Å resolution) features two binding motifs in the N lobe and one in the C lobe of hTF. Binding of Fe(N)hTF induces global and site-specific conformational changes within the TFR ectodomain. Specifically, movements at the TFR dimer interface appear to prime the TFR to undergo pH-induced movements that alter the hTF/TFR interaction. Iron release from each lobe then occurs by distinctly different mechanisms: Binding of His349 to the TFR (strengthened by protonation at low pH) controls iron release from the C lobe, whereas displacement of one N-lobe binding motif, in concert with the action of the dilysine trigger, elicits iron release from the N lobe. One binding motif in each lobe remains attached to the same α-helix in the TFR throughout the endocytic cycle. Collectively, the structure elucidates how the TFR accelerates iron release from the C lobe, slows it from the N lobe, and stabilizes binding of apohTF for return to the cell surface. Importantly, this structure provides new targets for mutagenesis studies to further understand and define this system.

PubMed: 21788477
DOI: 10.1073/pnas.1105786108

Experimental method

X-RAY DIFFRACTION (3.32 Å)