TAP1, a 70kDa transmembrane protein, and TAP2
are two structurally related subunits of the transporter associated
with antigen processing (TAP). The TAP complex is a member of the
ATP binding cassette (ABC) family of transmembrane transporters.
TAP1 and TAP2 each contain an N-terminal transmembrane region and
Cterminal nucleotide binding domains (NBD). TAP1 and TAP2 form
a complex in the endoplasmic reticulum (ER) membrane with the NBD
oriented in the cytosol. The TAP transporter is an essential component
of the MHC class I antigen presentation pathway by binding peptides
in its cytosolic part and subsequently translocating the peptides
into the lumen of the endoplasmic reticulum (ER) where assembly
of MHC class I and pepide takes place. Assembly of MHC class I-ß2-micorglobulin
(ß2-m) dimers in the ER involves 2 chaperones, calnexin which
interacts with free class I heavy (H) chains and calreticulin which
binds human class I-ß2 dimers prior to peptide loading. Calreticulin
remains associated with at least a subset of class I molecules
when they in turn bind to TAP . Polymorphic differences in MHC
class I H chains can results in quantitative as well as qualitative
differences in how they interact with peptide, ß2-m, calnexin,
calreticulin, ERp57, TAP and Tapasin, a subunit of the TAP complex
which binds to both TAP1 and MHC class I. Data obtained with Tapasin
deletion mutants revealed that binding to TAP is mediated by the
C-terminal region and that the N-terminal region is required to
stabilize the MHC class I loading complex. The Tapasin gene is
centromeric of HLA-DP locus between the HSET and HKE1.5 genes and
within 500 kbp of the transporters associated with antigen processing,
TAP1 and TAP2 genes. The localization of these genes within such
a short distance of each other on the chromosome implies some regulatory
or functional
significance.
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