2HAV

Apo-Human Serum Transferrin (Glycosylated)

Summary for 2HAV

• Entry DOI: 10.2210/pdb2hav/pdb
• Related: 1bp5
• Descriptor: Serotransferrin, CITRIC ACID, GLYCEROL (3 entities in total)
• Functional Keywords: serotransferrin, human, iron transporter, apo, iron-free, metal transport
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02787
• Total number of polymer chains: 2
• Total formula weight: 151659.53

Authors

Wally, J.,Everse, S.J. (deposition date: 2006-06-13, release date: 2006-06-27, Last modification date: 2023-08-30)

Primary citation

Wally, J.,Halbrooks, P.J.,Vonrhein, C.,Rould, M.A.,Everse, S.J.,Mason, A.B.,Buchanan, S.K.
The Crystal Structure of Iron-free Human Serum Transferrin Provides Insight into Inter-lobe Communication and Receptor Binding.
J.Biol.Chem., 281:24934-24944, 2006

PubMed Abstract: Serum transferrin reversibly binds iron in each of two lobes and delivers it to cells by a receptor-mediated, pH-dependent process. The binding and release of iron result in a large conformational change in which two subdomains in each lobe close or open with a rigid twisting motion around a hinge. We report the structure of human serum transferrin (hTF) lacking iron (apo-hTF), which was independently determined by two methods: 1) the crystal structure of recombinant non-glycosylated apo-hTF was solved at 2.7-A resolution using a multiple wavelength anomalous dispersion phasing strategy, by substituting the nine methionines in hTF with selenomethionine and 2) the structure of glycosylated apo-hTF (isolated from serum) was determined to a resolution of 2.7A by molecular replacement using the human apo-N-lobe and the rabbit holo-C1-subdomain as search models. These two crystal structures are essentially identical. They represent the first published model for full-length human transferrin and reveal that, in contrast to family members (human lactoferrin and hen ovotransferrin), both lobes are almost equally open: 59.4 degrees and 49.5 degrees rotations are required to open the N- and C-lobes, respectively (compared with closed pig TF). Availability of this structure is critical to a complete understanding of the metal binding properties of each lobe of hTF; the apo-hTF structure suggests that differences in the hinge regions of the N- and C-lobes may influence the rates of iron binding and release. In addition, we evaluate potential interactions between apo-hTF and the human transferrin receptor.

PubMed: 16793765
DOI: 10.1074/jbc.M604592200

Experimental method

X-RAY DIFFRACTION (2.7 Å)