Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains

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Item Type:	Article
Title:	Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains
Creators Name:	Daumke, O. and Knittler, M.R.
Abstract:	The ATP-binding-cassette (ABC) transporter associated with antigen processing (TAP) delivers peptides into the ER. TAP consists of two polypeptides (TAP1 and TAP2) each with an N-terminal transmembrane (TMD) and a C-terminal nucleotide binding domain (NBD). The two highly homologous NBDs of TAP show different nucleotide binding specificites, and identical mutations in the domains can have different effects on peptide transport. We asked whether this functional asymmetry of the NBDs is an intrinsic property or is imposed by the TMDs to which they are linked. To investigate the functional interdependence of the TAP domains, we created various TAP variants in which TMDs and/or NBDs were exchanged. All TAP variants except those with two TMDs of TAP1 could assemble. The TMDs did not affect the different nucleotide binding properties of the NBDs. The TAP variant with switched NBDs showed active peptide transport while the variants with pairs of identical NBDs or TMDs were inactive. Although both types of TMDs and NBDs have to be present for peptide transport they do not have to be assorted as in wild-type TAP. Thus, TAP domains seem to preserve functional autonomy despite their fusion into single polypeptide chains. We propose that the two NBDs act as nonequivalent 'modules' that directly determine the functional asymmetry of the included ATP-binding-cassettes. This provides a new insight into the function of NBDs and opens up new possibilities to investigate the molecular mechanism of the 'NBD engine' in ABC transporters.
Keywords:	Antigen Presentation, Transporter Associated with Antigen Presentation (TAP), Endoplasmic Reticulum, Peptide Transport, Nucleotide Binding Domains, Animals, Rats
Source:	European Journal of Biochemistry
ISSN:	0014-2956
Publisher:	Blackwell Publishing
Volume:	268
Number:	17
Page Range:	4776-86
Date:	September 2001
Official Publication:	https://doi.org/10.1046/j.1432-1327.2001.02406.x
PubMed:	View item in PubMed

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