PMID- 10600378
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20181130
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 294
IP  - 5
DP  - 1999 Dec 17
TI  - Kinetic analysis of peptide binding to the TAP transport complex: evidence for
      structural rearrangements induced by substrate binding.
PG  - 1203-13
AB  - The transporter associated with antigen processing (TAP) plays a key role in the 
      class I major histocompatibility complex (MHC) mediated immune surveillance. It
      translocates peptides generated by the proteasome complex into the endoplasmic
      reticulum (ER) for loading onto MHC class I molecules. At the cell surface these 
      MHC complexes are monitored for their antigenic cargo by cytotoxic T-lymphocytes.
      Peptide binding to TAP is the essential step for peptide selection and for
      subsequent ATP-dependent translocation into the ER lumen. To examine the pathway 
      of substrate recognition by TAP, we employed peptide epitopes, which were labeled
      with an environmentally sensitive fluorophore. Upon binding to TAP, a drastic
      fluorescence quenching of the fluorescent substrate was detected. This allowed us
      to analyze TAP function in real-time by using a homogeneous assay. Formation of
      the peptide-TAP complex is composed of a fast association step followed by a slow
      isomerization of the transport complex. Proton donor groups moving in proximity
      to the fluorescence label cause fluorescence quenching. Taken together, this
      peptide-induced structural reorganization may reflect the crosstalk of structural
      information between the peptide binding site and both nucleotide-binding domains 
      within the TAP complex.
CI  - Copyright 1999 Academic Press.
FAU - Neumann, L
AU  - Neumann L
AD  - Philipps-Universitat Marburg, Karl-von-Frisch-Str. 1, Marburg, 35033, Germany.
FAU - Tampe, R
AU  - Tampe R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Epitopes)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Peptides)
RN  - 0 (Protons)
RN  - 145892-13-3 (TAP2 protein, human)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - TPY09G7XIR (Fluorescein)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/*chemistry/immunology/*metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Allosteric Site
MH  - Amino Acid Sequence
MH  - Antigen Presentation/*immunology
MH  - Biological Transport
MH  - Epitopes/immunology/metabolism
MH  - Fluorescein/metabolism
MH  - Fluorescence
MH  - Fluorescent Dyes/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Isomerism
MH  - Kinetics
MH  - Models, Chemical
MH  - Peptides/immunology/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protons
MH  - Substrate Specificity
MH  - Thermodynamics
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1006/jmbi.1999.3329 [doi]
AID - S0022-2836(99)93329-6 [pii]
PST - ppublish
SO  - J Mol Biol. 1999 Dec 17;294(5):1203-13. doi: 10.1006/jmbi.1999.3329.