User:Mina Schneider/Sandbox
From Proteopedia
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The [https://en.wikipedia.org/wiki/Common_brushtail_possum '''common brushtail possum'''] ('''''Trichosurus Vulpecula''''') belongs to the [https://en.wikipedia.org/wiki/Metatheria '''metatherians'''], a mammalian clade, which diverged from placental mammals (like humains) approximately 130 million years ago. | The [https://en.wikipedia.org/wiki/Common_brushtail_possum '''common brushtail possum'''] ('''''Trichosurus Vulpecula''''') belongs to the [https://en.wikipedia.org/wiki/Metatheria '''metatherians'''], a mammalian clade, which diverged from placental mammals (like humains) approximately 130 million years ago. | ||
It includes all mammals with an '''abdominal pouche'''. Indeed, metatherians have invested in [https://en.wikipedia.org/wiki/Lactation '''lactation'''] (secretion of milk from the mammary glands), as opposed to placentation, as a way of rearing their young. | It includes all mammals with an '''abdominal pouche'''. Indeed, metatherians have invested in [https://en.wikipedia.org/wiki/Lactation '''lactation'''] (secretion of milk from the mammary glands), as opposed to placentation, as a way of rearing their young. | ||
| - | Reproduction in ''Trichosurus Vulpecula'' is typified by a short gestation (17 days) followed by a prolonged period of lactation (>200 days). Lactation is divided into at least three distinct phases between which milk composition changes dramatically <ref>J Demmer, I K Ross, M R Ginger, C K Piotte and M R Grigor, "Differential expression of milk protein genes during lactation in the common brushtail possum (Trichosurus vulpecula)", ''Journal of Molecular Endocrinology'' (1998) 20, 37–44</ref>., going along with a unique biology of the early development of young opossum. | + | Reproduction in ''Trichosurus Vulpecula'' is typified by a short gestation (17 days) followed by a prolonged period of lactation (>200 days). Lactation is divided into at least three distinct phases between which milk composition changes dramatically <ref>J Demmer, I K Ross, M R Ginger, C K Piotte and M R Grigor, "Differential expression of milk protein genes during lactation in the common brushtail possum (''Trichosurus vulpecula'')", ''Journal of Molecular Endocrinology'' (1998) 20, 37–44</ref>., going along with a unique biology of the early development of young opossum. |
'''Trichosurin''' is one of the three '''predomiant lipocalins''' found in the milk of ''Trichosurus Vulpecula''. | '''Trichosurin''' is one of the three '''predomiant lipocalins''' found in the milk of ''Trichosurus Vulpecula''. | ||
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=== Internal topology: A ligand-binding cavity === | === Internal topology: A ligand-binding cavity === | ||
| - | The trichosurin-binding cavity is a hydrophobic pocket with approximate dimensions of 11× 6×6 Å. The internal molecular surface is 425 Ų and encloses a total volume of ∼464 Å<sup>3</sup>. The cavity is constricted in the centre by the side chains of Phe65 and Phe114 which protrude into the pocket. | + | The trichosurin-binding cavity is a hydrophobic pocket with approximate dimensions of 11× 6×6 Å. The internal molecular surface is 425 Ų and encloses a total volume of ∼464 Å<sup>3</sup>. The cavity is constricted in the centre by the side chains of <scene name='75/750298/Phe_protrude/1'>Phe65 and Phe114/scene> which protrude into the pocket. |
Three asparagine residues, Asn49, Asn97 and Asn127 lie in the cavity and offer hydrogen-bonding sites for potential ligands. | Three asparagine residues, Asn49, Asn97 and Asn127 lie in the cavity and offer hydrogen-bonding sites for potential ligands. | ||
A few water molecules bind inside the barrel, near the top of the hydrophobic pocket. They form hydrogen bonds with the carbonyl oxygen of the amino acids. Those water molecules found within the predominantly non-polar pocket bring along the formation of water mediated ligand-to-protein hydrogen bonds <ref>D.E. Timm, L.J. Baker, H. Mueller, L. Zidel, M.V. Novotny, "Structural basis of pheromone binding to mouse major urinary protein (MUP-I)", ''Protein Science'' (2001) 10, 997–1004</ref>. | A few water molecules bind inside the barrel, near the top of the hydrophobic pocket. They form hydrogen bonds with the carbonyl oxygen of the amino acids. Those water molecules found within the predominantly non-polar pocket bring along the formation of water mediated ligand-to-protein hydrogen bonds <ref>D.E. Timm, L.J. Baker, H. Mueller, L. Zidel, M.V. Novotny, "Structural basis of pheromone binding to mouse major urinary protein (MUP-I)", ''Protein Science'' (2001) 10, 997–1004</ref>. | ||
Revision as of 16:17, 26 January 2017
Trichosurin : a Possum Milk Whey Lipocalin Protein
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The common brushtail possum (Trichosurus Vulpecula) belongs to the metatherians, a mammalian clade, which diverged from placental mammals (like humains) approximately 130 million years ago. It includes all mammals with an abdominal pouche. Indeed, metatherians have invested in lactation (secretion of milk from the mammary glands), as opposed to placentation, as a way of rearing their young. Reproduction in Trichosurus Vulpecula is typified by a short gestation (17 days) followed by a prolonged period of lactation (>200 days). Lactation is divided into at least three distinct phases between which milk composition changes dramatically [1]., going along with a unique biology of the early development of young opossum.
Trichosurin is one of the three predomiant lipocalins found in the milk of Trichosurus Vulpecula. And its high level of conservation in species that diverged approximatively 80 million years ago, due to continental separation, suggests that the function of trichosurin is critical in metatherian lactation.
Lipocalins are a large family of extracellular proteins that diverse in sequence but are structurally homologous. They bind and transport small hydrophobic molecules in a central hydrophobic pocket. The lipocalin family is defined by a common fold : an eight-stranded anti-parallel β-barrel with variable loop regions flanking and enclosing the top and bottom of the barrel, to form a hydrophobic pocket.
Contents |
Structural highlights
Trichosurin consists of 165 amino acids.
The two structures of trichosurin at both pH values 4.8 and 8.2 are very similar, with a root mean square difference in Cα atom positions of 0.54 Å over residues Leu24 to Cys166. The overall structural fold of trichosurin is an , anti-parallel β-barrel with a near the C-terminus which is common to all lipocalins. An extended loop region between β-strands A and B forms a which, together with residues on the between β-strands E and F, close one end of the barrel. Residues which are N-terminal to β-strand A pack against residues in the bottom of the barrel, effectively sealing the other end of the barrel. A , the last major conserved feature of the lipocalin fold, is formed between Cys73 and Cys166 and ties the C-terminus to β-strand D.
Trichosurin forms an unusual dimer. Trichosurin, of molecular mass approximatively equal to 38 kDa, has 905 Ų of surface area per monomer buried by dimerization. This represents 11.8% of the monomer surface. The core of the dimerization interface is made of the ring to ring association of . The aromatic interaction is further complemented with the hydrophobic burial of the side-chains of . Two interactions between Arg150 and Asp98 also contribute to the stability of the dimer along with numerous inter-molecular hydrogen bonds. At least fifteen water molecules are present within the dimer interface in the structure at pH 4.6. Its dimerization mode is conserved between both structures at pH 4.6 and pH 8.2. The orientation of the Tyr94 side chain does however change position in the higher pH structure, leading to a tighter closing of the barrel in this area of the pH 8.2 structure when compared with the main barrel.
The internal topology of the hydrophobic pocket is a key factor in the type and selectivity of binding, as is access to the binding pocket which is usually controlled by the loops formed by the residues between beta-strands at one end of the lipocalin beta-barrel.
Internal topology: A ligand-binding cavity
The trichosurin-binding cavity is a hydrophobic pocket with approximate dimensions of 11× 6×6 Å. The internal molecular surface is 425 Ų and encloses a total volume of ∼464 Å3. The cavity is constricted in the centre by the side chains of
