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Self-association of transmembrane domain 2 (TM2), but Not TM1, incCarnitine palmitoyltransferase 1A role of GXXXG(A) motifs
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Jenei, Zsuzsanna A., Borthwick, Karen, Zammit, Victor A. and Dixon, Ann M. (2009) Self-association of transmembrane domain 2 (TM2), but Not TM1, incCarnitine palmitoyltransferase 1A role of GXXXG(A) motifs. Journal of Biological Chemistry, Vol.284 (No.11). pp. 6988-6997. doi:10.1074/jbc.M808487200 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M808487200
Abstract
Carnitine palmitoyltransferase 1 (CPT1) controls the rate of entry of long-chain fatty acids into the mitochondrial matrix for beta-oxidation and has been reported to exist as an oligomer. We have investigated the in vivo oligomerization of full-length rat CPT1A (rCPT1A) along with those of the N-terminal truncation/deletion mutants Delta(1-82), Delta(1-18), and Delta(19-30) expressed in yeast mitochondria. The data indicate that in liver mitochondria in vivo CPT1A exists as a hexamer but that during preparation and storage of mitochondria the order of oligomerization is rapidly reduced to the trimer, such that a mixture of hexamer and trimer is observed in isolated mitochondria in vitro. Mutants bearing deletions of different segments of the N terminus (including the more N-terminal of the two transmembrane domains) have the same pattern of oligomerization when expressed in yeast mitochondria. The self-association of the individual rCPT1A transmembrane (TM) domains (TM1, TM2) was also studied using the TOXCAT assay (which measures TM self-association in the Escherichia coli inner membrane). There was minimal self-association of the sequence corresponding to TM1 but significant self-association of TM2 in TOXCAT. Chemical cross-linking and analytical ultracentrifugation of a TM2-derived synthetic peptide showed oligomerization with a similar trimer/hexamer equilibrium to that observed for native rCPT1A in isolated mitochondria. Therefore, there was a correlation between the oligomerization behavior of TM2 peptide and that of the full-length protein. In silico molecular modeling of rCPT1A TM2 highlighted the favorable orientation of GXXXG and GXXXA motifs in the formation of the TM2 hexamer.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Mitochondria, Oligomers, Biochemistry | ||||
| Journal or Publication Title: | Journal of Biological Chemistry | ||||
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. | ||||
| ISSN: | 0021-9258 | ||||
| Official Date: | 13 March 2009 | ||||
| Dates: |
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| Volume: | Vol.284 | ||||
| Number: | No.11 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 6988-6997 | ||||
| DOI: | 10.1074/jbc.M808487200 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||
| Funder: | Diabetes UK, University of Warwick Postgraduate Research Fellowship |
Data sourced from Thomson Reuters' Web of Knowledge
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