The transthyretin-related protein: structural investigation of a novel protein family.
The transthyretin-related protein (TRP) family comprises proteins predicted to be structurally related to the homotetrameric transport protein transthyretin (TTR). The function of TRPs is not yet fully established, but recent data suggest that they are involved in purine catabolism. We have determined the three-dimensional structure of the Escherichia coli TRP in two crystal forms; one at 1.65 A resolution in the presence of zinc, and the other at 2.1 A resolution in the presence of zinc and bromide. The structures revealed five zinc-ion-binding sites per monomer. Of these, the zinc ions bound at sites I and II are coordinated in tetrahedral geometries to the side chains of residues His9, His96, His98, Ser114, and three water molecules at the putative ligand-binding site. Of these four residues, His9, His98, and Ser114 are conserved. His9 and His98 bind the central zinc (site I) together with two water molecules. The side chain of His98 also binds to the zinc ion at site II. Bromide ions bind at site I only, replacing one of the water molecules coordinated to the zinc ion. The C-terminal four amino acid sequence motif Y-[RK]-G-[ST] constitutes the signature sequence of the TRP family. Two Tyr111 residues form direct hydrogen bonds to each other over the tetramer interface at the area, which in TTR constitutes the rear part of its thyroxine-binding channel. The putative substrate/ligand-binding channel of TRP is consequently shallower and broader than its counterpart in TTR.
Lundberg
Erik
E
Umeå Centre for Molecular Pathogenesis, Umeå University, SE-90187 Umeå, Sweden.
Bäckström
Stefan
S
Sauer
Uwe H
UH
Sauer-Eriksson
A Elisabeth
AE
D000595:Amino Acid Sequence; D001665:Binding Sites; D001965:Bromides / Q000378:metabolism; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D011228:Prealbumin / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D017967:Zinc Compounds / Q000378:metabolism
D001965:Bromides; D029968:Escherichia coli Proteins; D008024:Ligands; D011228:Prealbumin; D017967:Zinc Compounds; C093802:zinc bromide