Sandbox Reserved 1105: Difference between revisions
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== Human TTR structure with natural ligand : T4 and retinol == | == Human TTR structure with natural ligand : T4 and retinol == | ||
=== Human TTR | === Human TTR === | ||
Human TTR is a 54 kDa homo-tetramer, described as a dimer of dimer, rich in β-sheet. It is composed of 127 amino acids assembled around the central channel of the protein, resulting in a 222 symmetry protein. This tetramer contains a channel divided into two symmetry-related L-T4-binding sites. The channel has three sets of small depressions, termed halogen binding pockets (HBPs). They have a two-fold symmetry and confer a hydrophobic surface to the protein. But then, when the side chain of the TTR changes of conformation, these pockets can realise more hydrogen bonds with other molecules, they can be donor or acceptor. Thus, they are involved in the binding of the natural ligand, the thyroxine (T4). | Human TTR is a 54 kDa homo-tetramer, described as a dimer of dimer, rich in β-sheet. It is composed of 127 amino acids assembled around the central channel of the protein, resulting in a 222 symmetry protein. This tetramer contains a channel divided into two symmetry-related L-T4-binding sites. The channel has three sets of small depressions, termed halogen binding pockets (HBPs). They have a two-fold symmetry and confer a hydrophobic surface to the protein. But then, when the side chain of the TTR changes of conformation, these pockets can realise more hydrogen bonds with other molecules, they can be donor or acceptor. Thus, they are involved in the binding of the natural ligand, the thyroxine (T4). | ||
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==== TTR-RBP complex ==== | ==== TTR-RBP complex ==== | ||
TTR is a specific carrier of retinol-binding protein (RBP). | TTR is a specific carrier of retinol-binding protein (RBP). RBPs have a molecular mass of 21 kDa. They are composed of an eight-stranded β-barrel and a C-terminal α-helix. | ||
RBPs have a molecular mass of 21 kDa. They are composed of an eight-stranded β-barrel and a C-terminal α-helix. | |||
One tetramer of TTR can bind two molecules of RBP in vitro (1:2 stoichiometry). However, when we isolate the TTR-RBP complex from the plasma (in vivo) we find a 1:1 stoichiometry <ref name= "Naylor"> "Naylor, H. M., & Newcomer, M. E. (1999). The Structure of Human Retinol-Binding Protein (RBP) with Its Carrier Protein Transthyretin Reveals an Interaction with the Carboxy Terminus of RBP†,‡. Biochemistry, 38(9), 2647–2653. doi:10.1021/bi982291i"</ref> . The β-barrel entrance loop involved in A-B strands binding (amino acids from 31 to 38, hairpin1) is also implicated in the TTR-RBP interaction. | One tetramer of TTR can bind two molecules of RBP in vitro (1:2 stoichiometry). However, when we isolate the TTR-RBP complex from the plasma (in vivo) we find a 1:1 stoichiometry <ref name= "Naylor"> "Naylor, H. M., & Newcomer, M. E. (1999). The Structure of Human Retinol-Binding Protein (RBP) with Its Carrier Protein Transthyretin Reveals an Interaction with the Carboxy Terminus of RBP†,‡. Biochemistry, 38(9), 2647–2653. doi:10.1021/bi982291i"</ref> . The β-barrel entrance loop involved in A-B strands binding (amino acids from 31 to 38, hairpin1) is also implicated in the TTR-RBP interaction. | ||
RBP-TTR complex stale at high ionic strength and dissociate at low ionic strength <ref name="Zanetti"/>. It is explained by the presence of a hydrophobic surface in the contact region, represented by hairpin 1,2,3 (include Leu35, 63, 64 and 67). Trp67 (close to hairpin1) seems to be involved in the binding<ref name="Zanetti"/>. The dissociation constant of this complex is around 0.4 µM <ref name= "Naylor"/>. | RBP-TTR complex stale at high ionic strength and dissociate at low ionic strength <ref name ="Zanetti">Zanotti, G., Ottonello, S., Berni, R., & Monaco, H. L. (1993). Crystal Structure of the Trigonal Form of Human Plasma Retinol-binding Protein at 2·5 Å Resolution. Journal of Molecular Biology, 230(2), 613–624. doi:10.1006/jmbi.1993.1173 </ref>. It is explained by the presence of a hydrophobic surface in the contact region, represented by hairpin 1,2,3 (include Leu35, 63, 64 and 67). Trp67 (close to hairpin1) seems to be involved in the binding<ref name="Zanetti"/>. The dissociation constant of this complex is around 0.4 µM <ref name= "Naylor"/>. | ||
[[Image:images.png|thumb|Caption for the image]]] | |||
