1qab

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The structure of human retinol binding protein with its carrier protein transthyretin reveals interaction with the carboxy terminus of RBP

File:1qab.gif


1qab, resolution 3.20Å

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OverviewOverview

Whether ultimately utilized as retinoic acid, retinal, or retinol, vitamin, A is transported to the target cells as all-trans-retinol bound to, retinol-binding protein (RBP). Circulating in the plasma, RBP itself is, bound to transthyretin (TTR, previously referred to as thyroxine-binding, prealbumin). In vitro one tetramer of TTR can bind two molecules of, retinol-binding protein. However, the concentration of RBP in the plasma, is limiting, and the complex isolated from serum is composed of TTR and, RBP in a 1 to 1 stoichiometry. We report here the crystallographic, structure at 3.2 A of the protein-protein complex of human RBP and TTR., RBP binds at a 2-fold axis of symmetry in the TTR tetramer, and, consequently the recognition site itself has 2-fold symmetry: Four TTR, amino acids (Arg-21, Val-20, Leu-82, and Ile-84) are contributed by two, monomers. Amino acids Trp-67, Phe-96, and Leu-63 and -97 from RBP are, flanked by the symmetry-related side chains from TTR. In addition, the, structure reveals an interaction of the carboxy terminus of RBP at the, protein-protein recognition interface. This interaction, which involves, Leu-182 and Leu-183 of RBP, is consistent with the observation that, naturally occurring truncated forms of the protein are more readily, cleared from plasma than full-length RBP. Complex formation prevents, extensive loss of RBP through glomerular filtration, and the loss of, Leu-182 and Leu-183 would result in a decreased affinity of RBP for TTR.

About this StructureAbout this Structure

1QAB is a Protein complex structure of sequences from Homo sapiens with RTL as ligand. Full crystallographic information is available from OCA.

ReferenceReference

The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP., Naylor HM, Newcomer ME, Biochemistry. 1999 Mar 2;38(9):2647-53. PMID:10052934

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