Human lactoferrin: Difference between revisions
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The structure of LF<sub>N</sub> undergoes a dramatic conformational change upon iron binding. Upon iron binding, the two domains of LF<sub>N</sub> undergo a rigid 54.1º rotation about a <scene name='Sandbox_Reserved_302/Hinge/1'>screw axis</scene> that passes through Thr90 and Pro251.<ref name="gerstein">PMID:8230220</ref> | The structure of LF<sub>N</sub> undergoes a dramatic conformational change upon iron binding. Upon iron binding, the two domains of LF<sub>N</sub> undergo a rigid 54.1º rotation about a <scene name='Sandbox_Reserved_302/Hinge/1'>screw axis</scene> that passes through Thr90 and Pro251.<ref name="gerstein">PMID:8230220</ref> | ||
<jmol> | To visualize the <jmol> | ||
<jmolLink> | <jmolLink> | ||
<script>load files "=1CB6" "=1LCF";model 0;cartoon only;domain2 = {(92-249 or 1092-1249)}; | <script>load files "=1CB6" "=1LCF";model 0;cartoon only;domain2 = {(92-249 or 1092-1249)};select domain2 and _C;color green; | ||
structures = [{1.1}, {2.1}]; | structures = [{1.1}, {2.1}]; | ||
domains = [[{not domain2},{not domain2}, {alpha and not domain2 and not | domains = [[{not domain2},{not domain2}, {alpha and not domain2 and not altloc="B"}], [{domain2}, {(91,1091,250,1250) and *.CA}, {alpha and domain2 and not altloc="B"}],];moveto 1.0 { 880 471 63 56.8} 132.25 0.0 0.0 {2.646000000000001 15.972 -7.2715} 63.954979842981245 {0 0 0} 0 0 0 3.0 0.0 0.0; | ||
script "https://proteopedia.org/wiki/images/a/a2/Storymorph.spt";model 1;delay 0.5;model 2;delay 0.5;model 1; | script "https://proteopedia.org/wiki/images/a/a2/Storymorph.spt";superimpose(structures,domains,1);model 1;delay 0.5;model 2;delay 0.5;model 1; | ||
</script> | </script> | ||
<text>domain motion</text> | <text>domain motion</text> | ||
</jmolLink> | </jmolLink> | ||
</jmol> | </jmol>, we first load the two structures and superimpose them. You can choose a viewing orientation before pressing the morph button, which will visualize the conformational change from structure 1CB6 to 1LCF and back again<ref>The [[Jmol/Storymorph|Storymorph Jmol scripts]] creates the interpolated coordinates of the morph on the fly.</ref> | ||
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<jmol> | <jmol> | ||
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morph(15,structures,domains)</script> | morph(15,structures,domains)</script> | ||
<text>Morph</text> | <text>Morph</text> | ||
</jmolButton> | |||
</jmol> <jmol> | |||
<jmolButton> | |||
<script>select protein;spacefill only;</script> | |||
<text>spacefill</text> | |||
</jmolButton> | </jmolButton> | ||
</jmol> | </jmol> | ||
=Function & Application= | =Function & Application= | ||
Latest revision as of 18:56, 11 August 2021
Amino-Terminal Half-Molecule of Human LactoferrinHuman lactoferrin, LF, is a protein in the transferrin family. As such, it has the ability to tightly bind iron in conjunction with a large-scale conformational change associated with iron binding and release.[1] These properties give lactoferrin the ability to regulate iron, and possibly other metal, ion levels in the fluids and secretions, such as milk, of animals.[1] Lactoferrin is folded into two lobes: the N-terminal half, LFN (1dsn), and the C-terminal half, LFC. The two LF lobes have 37% homology and very similar tertiary structures; it has been suggested that the two lobes are the product of gene duplication.[2] Each lobe of LFN is further subdivided into two similarly sized α and β domains (Figure 1); the is situated in a deep cleft between the two domains.[1] In humans, lactoferrin is most abundant in milk, where it acts as part of the innate immune system.[3] Structure The amino-terminal half-molecule of human lactoferrin (LFN) is comprised of a single 333 amino acid chain divided into two similarly-sized α and β domains. The iron binding site is located within a deep cleft between the lobes, where iron is bound by of the α and β domains, respectively. Iron, which is bound to a carboxylate ion, is bound by Asp60, Ala123, and Gly124. Although unwound in LFN, form a helix when joined to LFC, forming the full LF protein.[1] The structure of LFN undergoes a dramatic conformational change upon iron binding. Upon iron binding, the two domains of LFN undergo a rigid 54.1º rotation about a that passes through Thr90 and Pro251.[4] To visualize the , we first load the two structures and superimpose them. You can choose a viewing orientation before pressing the morph button, which will visualize the conformational change from structure 1CB6 to 1LCF and back again[5] .
Function & ApplicationLike transferrin, lactoferrin is an iron binding molecule, capable of regulating iron levels in bodily fluids and secretions.[1] Unlike transferrin, only trace amounts of lactoferrin are found serum; however, lactoferrin can be found on concentrations ranging from 1 g/L to 7 g/L in milk.[3] In human milk, lactoferrin is a part of the innate immune system, demonstrating anti-microbial properties.[3][2] Many of lactoferrin's anti-microbial effects come from its ability to sequester iron, necessary for microbial growth.[2] Lactoferrin also exhibits anti-viral activity by binding to the key viral features of several viruses including hepatitis c virus, rotavirus, poliovirus, and HIV.[6] Because of the intrinsic antiviral properties of lactoferrin, it is of great interest as a drug delivery molecule. In this system, traditional antiviral medication, that can normally lead to a wide range of side-effects, can be targeted using lactoferrin, mitigating any ill effects.[6] External ResourcesLactoferrin at Wikipedia 3D structures of human lactoferrin |
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ReferencesReferences
- ↑ 1.0 1.1 1.2 1.3 1.4 Faber HR, Bland T, Day CL, Norris GE, Tweedie JW, Baker EN. Altered domain closure and iron binding in transferrins: the crystal structure of the Asp60Ser mutant of the amino-terminal half-molecule of human lactoferrin. J Mol Biol. 1996 Feb 23;256(2):352-63. PMID:8594202
- ↑ 2.0 2.1 2.2 Farnaud S, Evans RW. Lactoferrin--a multifunctional protein with antimicrobial properties. Mol Immunol. 2003 Nov;40(7):395-405. PMID:14568385
- ↑ 3.0 3.1 3.2 Sanchez L, Calvo M, Brock JH. Biological role of lactoferrin. Arch Dis Child. 1992 May;67(5):657-61. PMID:1599309
- ↑ Gerstein M, Anderson BF, Norris GE, Baker EN, Lesk AM, Chothia C. Domain closure in lactoferrin. Two hinges produce a see-saw motion between alternative close-packed interfaces. J Mol Biol. 1993 Nov 20;234(2):357-72. PMID:8230220 doi:http://dx.doi.org/10.1006/jmbi.1993.1592
- ↑ The Storymorph Jmol scripts creates the interpolated coordinates of the morph on the fly.
- ↑ 6.0 6.1 van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res. 2001 Dec;52(3):225-39. PMID:11675140
Page originally authored by Christian Axen