title: Iron and bismuth bound human serum transferrin reveals a partially-opened conformation in the N-lobe.
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.
authors.affiliation: Department of Chemistry, the University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhang
authors.forename: Minji
authors.initials: M
authors.lastname: Wang
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Sun
mesh_terms: D001665:Binding Sites; D001692:Biological Transport / Q000502:physiology; D001729:Bismuth / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014168:Transferrin; D007501:Iron; D001729:Bismuth