Dataset Information

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.

SUBMITTER: Yang N

PROVIDER: S-EPMC3525939 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Yang Nan N Zhang Hongmin H Zhang Hongmin H Wang Minji M Hao Quan Q Sun Hongzhe H

Scientific reports 20121219

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 ...[more]

PMID: 23256035

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Dataset Information

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

Publications

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

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