2hav
From Proteopedia
Line 4: | Line 4: | ||
|PDB= 2hav |SIZE=350|CAPTION= <scene name='initialview01'>2hav</scene>, resolution 2.7Å | |PDB= 2hav |SIZE=350|CAPTION= <scene name='initialview01'>2hav</scene>, resolution 2.7Å | ||
|SITE= | |SITE= | ||
- | |LIGAND= <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene> | + | |LIGAND= <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
+ | |DOMAIN= | ||
+ | |RELATEDENTRY=[[1bp5|1bp5]] | ||
+ | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hav FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hav OCA], [http://www.ebi.ac.uk/pdbsum/2hav PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hav RCSB]</span> | ||
}} | }} | ||
Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
- | |||
- | ==Disease== | ||
- | Known diseases associated with this structure: Atransferrinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190000 190000]], Iron deficiency anemia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190000 190000]] | ||
==About this Structure== | ==About this Structure== | ||
Line 27: | Line 27: | ||
[[Category: Everse, S J.]] | [[Category: Everse, S J.]] | ||
[[Category: Wally, J.]] | [[Category: Wally, J.]] | ||
- | [[Category: CIT]] | ||
- | [[Category: GOL]] | ||
[[Category: apo]] | [[Category: apo]] | ||
[[Category: human]] | [[Category: human]] | ||
Line 35: | Line 33: | ||
[[Category: serotransferrin]] | [[Category: serotransferrin]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:27:54 2008'' |
Revision as of 00:28, 31 March 2008
| |||||||
, resolution 2.7Å | |||||||
---|---|---|---|---|---|---|---|
Ligands: | , | ||||||
Related: | 1bp5
| ||||||
Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
Apo-Human Serum Transferrin (Glycosylated)
Overview
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.
About this Structure
2HAV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of iron-free human serum transferrin provides insight into inter-lobe communication and receptor binding., Wally J, Halbrooks PJ, Vonrhein C, Rould MA, Everse SJ, Mason AB, Buchanan SK, J Biol Chem. 2006 Aug 25;281(34):24934-44. Epub 2006 Jun 22. PMID:16793765
Page seeded by OCA on Mon Mar 31 03:27:54 2008