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| - | [[Image:1jqf.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1jqf| PDB=1jqf | SCENE= }} | | {{STRUCTURE_1jqf| PDB=1jqf | SCENE= }} |
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| - | '''Human Transferrin N-Lobe Mutant H249Q'''
| + | ===Human Transferrin N-Lobe Mutant H249Q=== |
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| - | ==Overview==
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| - | Proteins of the transferrin (Tf) family play a central role in iron homeostasis in vertebrates. In vertebrate Tfs, the four iron-binding ligands, 1 Asp, 2 Tyr, and 1 His, are invariant in both lobes of these bilobal proteins. In contrast, there are striking variations in the Tfs that have been characterized from insect species; in three of them, sequence changes in the C-lobe binding site render it nonfunctional, and in all of them the His ligand in the N-lobe site is changed to Gln. Surprisingly, mutagenesis of the histidine ligand, His249, to glutamine in the N-lobe half-molecule of human Tf (hTf/2N) shows that iron binding is destabilized and suggests that Gln249 does not bind to iron. We have determined the crystal structure of the H249Q mutant of hTf/2N and refined it at 1.85 A resolution (R = 0.221, R(free) = 0.246). The structure reveals that Gln249 does coordinate to iron, albeit with a lengthened Fe-Oepsilon1 bond of 2.34 A. In every other respect, the protein structure is unchanged from wild-type. Examination of insect Tf sequences shows that the K206.K296 dilysine pair, which aids iron release from the N-lobes of vertebrate Tfs, is not present in the insect proteins. We conclude that substitution of Gln for His does destabilize iron binding, but in the insect Tfs this is compensated by the loss of the dilysine interaction. The combination of a His ligand with the dilysine pair in vertebrate Tfs may have been a later evolutionary development that gives more sophisticated pH-mediated control of iron release from the N-lobe of transferrins.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11570867}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11570867 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11570867}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Mason, A B.]] | | [[Category: Mason, A B.]] |
| | [[Category: Iron binding protein]] | | [[Category: Iron binding protein]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:38:38 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:38:39 2008'' |
Revision as of 17:38, 1 July 2008
Template:STRUCTURE 1jqf
Human Transferrin N-Lobe Mutant H249Q
Template:ABSTRACT PUBMED 11570867
About this Structure
1JQF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Ligand variation in the transferrin family: the crystal structure of the H249Q mutant of the human transferrin N-lobe as a model for iron binding in insect transferrins., Baker HM, Mason AB, He QY, MacGillivray RT, Baker EN, Biochemistry. 2001 Oct 2;40(39):11670-5. PMID:11570867
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