RGD Reference Report - Biogenesis of functional antigenic peptide transporter TAP requires assembly of pre-existing TAP1 with newly synthesized TAP2. - Rat Genome Database

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Biogenesis of functional antigenic peptide transporter TAP requires assembly of pre-existing TAP1 with newly synthesized TAP2.

Authors: Keusekotten, K  Leonhardt, RM  Ehses, S  Knittler, MR 
Citation: Keusekotten K, etal., J Biol Chem. 2006 Jun 30;281(26):17545-51. Epub 2006 Apr 19.
RGD ID: 2312375
Pubmed: PMID:16624807   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M602360200   (Journal Full-text)

The transporter associated with antigen processing (TAP) is essential for the delivery of antigenic peptides from the cytosol into the endoplasmic reticulum (ER), where they are loaded onto major histocompatibility complex class I molecules. TAP is a heterodimeric transmembrane protein that comprises the homologous subunits TAP1 and TAP2. As for many other oligomeric protein complexes, which are synthesized in the ER, the process of subunit assembly is essential for TAP to attain a native functional state. Here, we have analyzed the individual requirements of TAP1 and TAP2 for the formation of a functional TAP complex. Unlike TAP1, TAP2 is very unstable when expressed in isolation. We show that heterodimerization of TAP subunits is required for maintaining a stable level of TAP2. By using an in vitro expression system we demonstrate that the biogenesis of functional TAP depends on the assembly of preexisting TAP1 with newly synthesized TAP2, but not vice versa. The pore forming core transmembrane domain (core TMD) of in vitro expressed TAP2 is necessary and sufficient to allow functional complex formation with pre-existing TAP1. We propose that the observed assembly mechanism of TAP protects newly synthesized TAP2 from rapid degradation and controls the number of transport active transporter molecules. Our findings open up new possibilities to investigate functional and structural properties of TAP and provide a powerful model system to address the biosynthetic assembly of oligomeric transmembrane proteins in the ER.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
identical protein binding  IPITap2 (Rattus norvegicus)2312375homodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tap2  (transporter 2, ATP binding cassette subfamily B member)

Objects referenced in this article
Gene Tap1 transporter 1, ATP binding cassette subfamily B member Rattus norvegicus

Additional Information