Abstract
Within the adaptive immune system the transporter associated with antigen processing (TAP) plays a pivotal role in loading of peptides onto major histocompatibility (MHC) class I molecules. As a central tool to investigate the structure and function of the TAP complex, we created cysteine-less human TAP subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2. After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC class I molecules to the cell surface.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP Binding Cassette Transporter, Subfamily B, Member 3
-
ATP-Binding Cassette Transporters / chemistry*
-
ATP-Binding Cassette Transporters / genetics*
-
ATP-Binding Cassette Transporters / metabolism
-
Adenosine Triphosphate / metabolism
-
Amino Acid Substitution
-
Antigen Presentation
-
Biological Transport, Active
-
Cell Line
-
Cysteine / chemistry
-
Histocompatibility Antigens Class I / metabolism
-
Humans
-
Models, Molecular
-
Protein Subunits
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Transfection
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP Binding Cassette Transporter, Subfamily B, Member 3
-
ATP-Binding Cassette Transporters
-
Histocompatibility Antigens Class I
-
Protein Subunits
-
Recombinant Proteins
-
TAP1 protein, human
-
TAP2 protein, human
-
Adenosine Triphosphate
-
Cysteine