Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TAP delivers antigenic peptides into the endoplasmic reticulum (ER) that are subsequently bound by MHC class I molecules. TAP consists of two subunits (TAP1 and TAP2), each with a transmembrane (TMD) and a nucleotide-binding (NBD) domain. The two TAP-NBDs have distinct biochemical properties and control different steps during the peptide translocation process. We noted previously that the nonhomologous C-terminal tails of rat TAP1 and TAP2 determine the distinct functions of TAP-NBD1 and -NBD2. To identify the sequence elements responsible for the asymmetrical NBD function, we constructed chimeric rat TAP variants in which we systematically exchanged sequence regions of different length between the two TAP-NBDs. Our fine-mapping studies demonstrate that a nonhomologous region containing the alpha6/beta10-loop in conjunction with the downstream switch region is directly responsible for the functional separation of the TAP-NBDs. The alpha6/beta10-loop determines the nonsynonymous nucleotide binding of NBD1 and NBD2, whereas the switch region seems to play a critical role in regulating the functional cross-talk between the structural domains of TAP. Based on our findings, we postulate that these two sequence elements build a minimal functional unit that controls the asymmetry of the two TAP-NBDs.
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PMID:Functional role of C-terminal sequence elements in the transporter associated with antigen processing. 1561 Dec 56