User:Ona Ambrozaite/Sandbox 1
From Proteopedia
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[[Image:Trichosurin_for_ProtPedia.png|300px|center|thumb| Structure of the Possum Milk Whey Lipocalin Trichosurin at pH 8.2]] | [[Image:Trichosurin_for_ProtPedia.png|300px|center|thumb| Structure of the Possum Milk Whey Lipocalin Trichosurin at pH 8.2]] | ||
| - | The fully functional trichosurin consists of two monomers joining to form a dimer of identical eight-stranded, anti-parallel β-barrels. The study of lipocalin dimerization modes has shown six variations in orientation, with trichosurin adding a seventh one to the list. Overall, there are four main chains (A, B, C, and D), in the dimer, with each chain a length of 166 amino acids. There is also a signal sequence at the N-terminus of the chain that is cleaved before a fully functional molecule is formed. Currently, there are two crystal structures of trichosurin that can be found at RCSB, one determined at pH 8.2 and another at a lower pH of 4.6. | + | The fully functional trichosurin consists of two monomers joining to form a dimer of identical eight-stranded, anti-parallel β-barrels <ref>PMID: 11058743</ref>. The study of lipocalin dimerization modes has shown six variations in orientation, with trichosurin adding a seventh one to the list. Overall, there are four main chains (A, B, C, and D), in the dimer, with each chain a length of 166 amino acids. There is also a signal sequence at the N-terminus of the chain that is cleaved before a fully functional molecule is formed. Currently, there are two crystal structures of trichosurin that can be found at RCSB, one determined at pH 8.2 and another at a lower pH of 4.6. |
With regards to the binding cavity, there are the three asparagine residues, Asn49, Asn97 and Asn127, which lie in the pocket and offer hydrogen-bonding sites for a potential ligand, especially Asn49. The shape and charge distribution within the pocket suggest that small hydrophobic molecules can be accommodated within, with such sites providing the necessary hydrogen bonding opportunities. | With regards to the binding cavity, there are the three asparagine residues, Asn49, Asn97 and Asn127, which lie in the pocket and offer hydrogen-bonding sites for a potential ligand, especially Asn49. The shape and charge distribution within the pocket suggest that small hydrophobic molecules can be accommodated within, with such sites providing the necessary hydrogen bonding opportunities. | ||
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As expected for an extracellular protein, trichosurin displays a large amount of hydrophilic surface area, with the more hydrophobic areas between the helix, the outside of the barrel, and the dimer interface where ligands such as 2-naphthol can bind. The binding site is found in the centre of the β-barrel and can be occupied by water and isopropanol molecules from the corresponding crystallization medium. In fact, researchers were able to crystallize trichosurin with 2-naphthol and 4-ethylphenol, the presence of which provides clues to the function of trichosurin. | As expected for an extracellular protein, trichosurin displays a large amount of hydrophilic surface area, with the more hydrophobic areas between the helix, the outside of the barrel, and the dimer interface where ligands such as 2-naphthol can bind. The binding site is found in the centre of the β-barrel and can be occupied by water and isopropanol molecules from the corresponding crystallization medium. In fact, researchers were able to crystallize trichosurin with 2-naphthol and 4-ethylphenol, the presence of which provides clues to the function of trichosurin. | ||
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Overall, trichosurin follows the general lipocalin superfamily fold pattern by having a β-barrel, several extended loop regions between β strands that close the ends of the barrel, a helix near the C-terminus which is common to all lipocalins, and a major conserved feature of the lipocalin fold, a disulfide bond, formed by two cysteines (Cys73 and Cys166 ) in each chain that ties the C-terminus to the corresponding β-strand. | Overall, trichosurin follows the general lipocalin superfamily fold pattern by having a β-barrel, several extended loop regions between β strands that close the ends of the barrel, a helix near the C-terminus which is common to all lipocalins, and a major conserved feature of the lipocalin fold, a disulfide bond, formed by two cysteines (Cys73 and Cys166 ) in each chain that ties the C-terminus to the corresponding β-strand. | ||
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Trichosurin has 34% amino acid identity to the rodent major urinary proteins (MUPs ) and 28% amino acid identity to the major horse dander allergen equc1. Tichosurin homologues have been identified in both the tammar wallaby and the South American opossum (77% amino acid identity). Such high level of conservation in species that diverged about 80 million years ago suggests that the function of trichosurin is critical in metatherian lactation. | Trichosurin has 34% amino acid identity to the rodent major urinary proteins (MUPs ) and 28% amino acid identity to the major horse dander allergen equc1. Tichosurin homologues have been identified in both the tammar wallaby and the South American opossum (77% amino acid identity). Such high level of conservation in species that diverged about 80 million years ago suggests that the function of trichosurin is critical in metatherian lactation. | ||
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With regards to structural comparison with other lipocalins such as bovine BLG that is a prototypic milk lipocalin, trichosurin shows great similarity. This is because structural alignment of trichosurin, expressed in E. coli and crystallized at pH 4.8, with the BLG structure 1BEB yielded an rmsd of 2.76 Å over 139 equivalent residues. | With regards to structural comparison with other lipocalins such as bovine BLG that is a prototypic milk lipocalin, trichosurin shows great similarity. This is because structural alignment of trichosurin, expressed in E. coli and crystallized at pH 4.8, with the BLG structure 1BEB yielded an rmsd of 2.76 Å over 139 equivalent residues. | ||
== Relevance == | == Relevance == | ||
| - | Trichosurin, an important marsupial milk protein, is highly conserved across metatherians. The opossum, a metatherian, shares a common ancestor with humans around 130 million years ago, is of particular importance to study the differences between the development of metatherians and other mammals. In opossums, lactation is divided into three stages that each have a very unique milk composition, and trichosurin is one of three predominant lipocalins found in the milk of T. vulpecula. | + | Trichosurin, an important marsupial milk protein, is highly conserved across metatherians. The opossum, a metatherian, shares a common ancestor with humans around 130 million years ago, is of particular importance to study the differences between the development of metatherians and other mammals. In opossums, lactation is divided into three stages that each have a very unique milk composition, and trichosurin is one of three predominant lipocalins found in the milk of T. vulpecula <ref>PMID: 2636424</ref>, <ref>PMID: 9493361</ref>. |
It is known that phenolic compounds are found in plants and used to deter herbivores, including possums, who then have to metabolize these compounds. It has also been shown that female possums concentrate phenolic compounds in their milk, which could act as a priming source for the young's liver to produce detoxifying enzymes that they can then use to survive while eating toxic plant sources. | It is known that phenolic compounds are found in plants and used to deter herbivores, including possums, who then have to metabolize these compounds. It has also been shown that female possums concentrate phenolic compounds in their milk, which could act as a priming source for the young's liver to produce detoxifying enzymes that they can then use to survive while eating toxic plant sources. | ||
Revision as of 23:51, 6 March 2020
Trichosurin
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