Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator.
The transporter associated with antigen processing (TAP) delivers peptides to the lumen of the endoplasmic reticulum in an adenosine triphosphate (ATP) dependent fashion for presentation by major histocompatibility complex class I molecules. We show that the mouse TAP translocator (H-2b haplotype) selects peptides based on a minimal size of nine residues, and on the presence of a hydrophobic COOH-terminal amino acid. The preponderance of COOH-terminal hydrophobic amino acids in peptides capable of binding to mouse class I molecules thus fits remarkably well with the specificity of the TAP translocator. In addition to transport in the lumenal direction, efflux of peptide in the cytosolic direction is observed in an ATP- and temperature-dependent manner. By maintaining a low peptide concentration at the site of class I assembly, this efflux mechanism may ensure that class I molecules are loaded preferentially with high affinity peptides.
Schumacher
T N
TN
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Kantesaria
D V
DV
Heemels
M T
MT
Ashton-Rickardt
P G
PG
Shepherd
J C
JC
Fruh
K
K
Yang
Y
Y
Peterson
P A
PA
Tonegawa
S
S
Ploegh
H L
HL
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013696:Temperature
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human; D000255:Adenosine Triphosphate