Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing

Abstract

The transporter associated with antigen processing (TAP) is an ABC transporter formed of two subunits, TAP1 and TAP2, each of which has an N-terminal membrane-spanning domain and a C-terminal ABC ATPase domain. We report the structure of the C-terminal ABC ATPase domain of TAP1 (cTAP1) bound to ADP. cTAP1 forms an L-shaped molecule with two domains, a RecA-like domain and a small a-helical domain. The diphosphate group of ADP interacts with the P-loop as expected. Residues thought to be involved in g-phosphate binding and hydrolysis show¯exibility in the ADP-bound state as evidenced by their high B-factors. Comparisons of cTAP1 with other ABC ATPases from the ABC transporter family as well as ABC ATPases involved in DNA maintenance and repair reveal key regions and residues speci®c to each family. Three ATPase subfamilies are identi®ed which have distinct adenosine recognition motifs, as well as distinct subdomains that may be speci®c to the different functions of each subfamily. Differences between TAP1 and TAP2 in the nucleotide-binding site may be related to the observed asymmetry during peptide transport.

The CFTR Ion Channel: Gating, Regulation, and Anion Permeation

“…Third, the side chain of the Walker B aspartate (D572 in NBD1 and D1370 in NBD2 of CFTR) coordinates the Mg 2þ ion. These structural studies of ABC proteins in the past decade (Hung et al 1998;Diederichs et al 2000;Gaudet and Wiley 2001;Karpowich et al 2001;Yuan et al 2001;Smith et al 2002;Chen et al 2003;Schmitt et al 2003;Verdon et al 2003;Lewis et al 2004Lewis et al , 2005 have provided rich molecular details that can be applied to facilitate functional exploration of CFTR. For example, Zhou et al (2006) used site-directed mutagenesis and high-resolution single-channel recording to investigate the contribution of the aromatic residues W401 in NBD1 and Y1219 in NBD2 that interact with the adenine ring of ATP.…”

The motor domains of ABC-transporters

“…Elevated B factors are thus indicative of high flexibility. One striking aspect when looking at the data of the TAP1 monomer NBD structure, are elevated B-factors (Gaudet and Wiley 2001). Interestingly, in the TAP1 structure, where the NBD is complexed with Mg*ADP, two regions of high mobility can be identified.…”

Molecular Basis for Differential Nucleotide Binding of the Nucleotide-Binding Domain of ABC-Transporter CvaB

“…In an active ABC transporter, ATP-hydrolysis is widely assumed to supply energy to (14)(15)(16)27,28) for the translocation process. Many crystal structures of the ABC-NBD are stabilized by binding ADP or ATP analogs (6,29,30), and site-directed mutagenesis of the conserved binding sites will affect the binding and hydrolysis of nucleotide (31). Biochemical studies indicated that the bound ATP interacted extensively with the HlyB-NBD nucleotide-binding sites (6,24), induced the dimerization of the protein (26,32), and showed cooperation in the ATP hydrolysis (25).…”

“…The HlyB-NBD dimer structure provided the ATP and Mg as templates to generate the ATP and GTP-bound models of CvaB-NBD. The ligand structure (Mg and ADP) of TAP1-NBD (PDB entry 1JJ7) (29) were also considered when docking nucleotides onto CvaB-NBD. A discrete water model was used to treat solvation.…”