Database accession: MF4110001
Name: Transthyretin (rat)
PDB ID: 1gke
Experimental method: X-ray (2.50 Å)
Assembly: homotetramer (dimer of dimers)
Source organism: Rattus norvegicus
Primer publication of the structure:
Wojtczak A
Crystal structure of rat transthyretin at 2.5 A resolution: first report on a unique tetrameric structure.
(1997) Acta Biochim. Pol. 44: 505-17
PMID: 9511961
Abstract:
The first observation of a unique tetrameric molecular structure of transthyretin from rat (rTTR, prealbumin) is reported. The structure has been determined by X-ray diffraction using molecular replacement and the structure of human transthyretin (hTTR) as a starting model. Crystals of native rat transthyretin are tetragonal, space group P4(3)2(1)2, and have four independent monomers in the asymmetric unit of the crystal lattice. Data were collected to 2.5 A resolution and the structure has been refined to R = 18.9% for 13584 data points between 8-2.5 A resolution. Like hTTR, the rat protein is also a 54000 Da tetramer with four identical polypeptide chains of 127 amino-acid residues. Of the 22 amino-acid residues which are different in the human and rat TTR sequences, none are in the thyroxine binding domain. Analysis of these data reveal that the tertiary structure of rTTR is similar to that of hTTR with only small differences in the flexible loop regions on the surface of the protein. As a result of local changes in flexible loop regions near residues 30-41, 60-65 and 102-104, the structure of rTTR monomers is more compact than that of the corresponding hTTR monomers. The loop between residues 30-41 is bound closer to the monomer core in the former as compared with the latter structure and there is a wider opening of the space formed between these loops at two adjacent monomeric subunits. These conformational changes do not affect the interfaces between the monomeric subunits and are not transmitted to the thyroxine binding site so that its topology remains not altered.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
identical protein binding Interacting selectively and non-covalently with an identical protein or proteins.
protein heterodimerization activity Interacting selectively and non-covalently with a nonidentical protein to form a heterodimer.
thyroid hormone binding Interacting selectively and non-covalently with thyroxine (T4) or triiodothyronine (T3), tyrosine-based hormones produced by the thyroid gland.
Biological process:
thyroid hormone transport The directed movement of thyroid hormone into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
retinol metabolic process The chemical reactions and pathways involving retinol, one of the three compounds that makes up vitamin A.
thyroid hormone metabolic process The chemical reactions and pathways involving any of the compounds secreted by the thyroid gland, largely thyroxine and triiodothyronine.
Cellular component:
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
Structural annotations of the participating protein chains.Entry contents: 4 distinct polypeptide molecules
Chains: A, B, C, D
Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
Number of unique protein segments: 1
Name: Transthyretin
Source organism: Rattus norvegicus
Length: 120 residues
Sequence:Sequence according to PDB SEQRESSKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
UniProtKB AC: P02767 (positions: 28-147) Coverage: 81.6%
UniRef90 AC: UniRef90_P02767 (positions: 28-147)
Name: Transthyretin
Source organism: Rattus norvegicus
Length: 120 residues
Sequence:Sequence according to PDB SEQRESSKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
UniProtKB AC: P02767 (positions: 28-147) Coverage: 81.6%
UniRef90 AC: UniRef90_P02767 (positions: 28-147)
Name: Transthyretin
Source organism: Rattus norvegicus
Length: 120 residues
Sequence:Sequence according to PDB SEQRESSKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
UniProtKB AC: P02767 (positions: 28-147) Coverage: 81.6%
UniRef90 AC: UniRef90_P02767 (positions: 28-147)
Name: Transthyretin
Source organism: Rattus norvegicus
Length: 120 residues
Sequence:Sequence according to PDB SEQRESSKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN
UniProtKB AC: P02767 (positions: 28-147) Coverage: 81.6%
UniRef90 AC: UniRef90_P02767 (positions: 28-147)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Complex evidence:
Transthyretin was shown in calorimetrics experiments to follow two-state folding/binding kinetics with the emergence of structure being linked to oligomerization (PMID: 11152276).
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). 