| Structural highlights
Function
[TRFL_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.[1] [2] Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration.[3] [4] Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.[5] [6] The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.[7] [8] Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.[9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The three-dimensional structure of a form of human apolactoferrin, in which one lobe (the N-lobe) has an open conformation and the other lobe (the C-lobe) is closed, has been refined at 2.0 A resolution. The refinement, by restrained least-squares methods, used synchrotron radiation X-ray diffraction data combined with a lower resolution diffractometer data set. The final refined model (5346 protein atoms from residues 1-691, two Cl- ions and 363 water molecules) gives a crystallographic R factor of 0.201 (Rfree = 0. 286) for all 51305 reflections in the resolution range 10.0-2.0 A. The conformational change in the N-lobe, which opens up the binding cleft, involves a 54 degrees rotation of the N2 domain relative to the N1 domain. This also results in a small reorientation of the two lobes relative to one another with a further approximately 730 A2 of surface area being buried as the N2 domain contacts the C-lobe and the inter-lobe helix. These new contacts also involve the C-terminal helix and provide a mechanism through which the conformational and iron-binding status of the N-lobe can be signalled to the C-lobe. Surface-area calculations indicate a fine balance between open and closed forms of lactoferrin, which both have essentially the same solvent-accessible surface. Chloride ions are bound in the anion-binding sites of both lobes, emphasizing the functional significance of these sites. The closed configuration of the C-lobe, attributed in part to weak stabilization by crystal packing interactions, has important implications for lactoferrin dynamics. It shows that a stable closed structure, essentially identical to that of the iron-bound form, can be formed in the absence of iron binding.
Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change.,Jameson GB, Anderson BF, Norris GE, Thomas DH, Baker EN Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 2):1319-35. PMID:10089508[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Jameson GB, Anderson BF, Norris GE, Thomas DH, Baker EN. Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change. Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 2):1319-35. PMID:10089508
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