1QAB

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

Summary for 1QAB

• Entry DOI: 10.2210/pdb1qab/pdb
• Descriptor: PROTEIN (transthyretin), PROTEIN (retinol binding protein), RETINOL (3 entities in total)
• Functional Keywords: human serum retinol binding protein, transthyretin, prealbumin, transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P02766 P02753
• Total number of polymer chains: 6
• Total formula weight: 96554.13

Authors

Naylor, H.M.,Newcomer, M.E. (deposition date: 1999-02-03, release date: 1999-02-16, Last modification date: 2024-11-13)

Primary citation

Naylor, H.M.,Newcomer, M.E.
The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP.
Biochemistry, 38:2647-2653, 1999

PubMed Abstract: 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.

PubMed: 10052934
DOI: 10.1021/bi982291i

Experimental method

X-RAY DIFFRACTION (3.2 Å)