Iron and bismuth bound human serum transferrin reveals a partially-opened conformation in the N-lobe

Sci Rep. 2012:2:999. doi: 10.1038/srep00999. Epub 2012 Dec 19.

Abstract

Human serum transferrin (hTF) binds Fe(III) tightly but reversibly, and delivers it to cells via a receptor-mediated endocytosis process. The metal-binding and release result in significant conformational changes of the protein. Here, we report the crystal structures of diferric-hTF (Fe(N)Fe(C)-hTF) and bismuth-bound hTF (Bi(N)Fe(C)-hTF) at 2.8 and 2.4 Å resolutions respectively. Notably, the N-lobes of both structures exhibit unique "partially-opened" conformations between those of the apo-hTF and holo-hTF. Fe(III) and Bi(III) in the N-lobe coordinate to, besides anions, only two (Tyr95 and Tyr188) and one (Tyr188) tyrosine residues, respectively, in contrast to four residues in the holo-hTF. The C-lobe of both structures are fully closed with iron coordinating to four residues and a carbonate. The structures of hTF observed here represent key conformers captured in the dynamic nature of the transferrin family proteins and provide a structural basis for understanding the mechanism of metal uptake and release in transferrin families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Biological Transport / physiology
  • Bismuth / chemistry*
  • Bismuth / metabolism
  • Crystallography, X-Ray
  • Humans
  • Iron / chemistry*
  • Iron / metabolism
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Transferrin / chemistry*
  • Transferrin / metabolism

Substances

  • Transferrin
  • Iron
  • Bismuth