3S9L: Complex Between Transferrin Receptor 1 And Transferrin With Iron In The N-Lobe, Cryocooled 2

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-A 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 alpha-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.
PDB ID: 3S9LDownload
MMDB ID: 92602
PDB Deposition Date: 2011/6/1
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 3.22  Å
Source Organism:
Similar Structures:
Biological Unit for 3S9L: tetrameric; determined by author
Molecular Components in 3S9L
Label Count Molecule
Proteins (4 molecules)
Transferrin Receptor Protein 1(Gene symbol: TFRC)
Molecule annotation
Serotransferrin(Gene symbol: TF)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB