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Mechanism of action of TgsGP

Posted by Yassum on 07 Oct 2013 at 09:36 GMT

This paper comes a bit later than the one published by our group in Nature, titled "Mechanism of Trypanosoma brucei gambiense resistance to human serum" (PMID: 23965626 ; doi: 10.1038/nature12516). It supports the observations that were made, but doesn't go as far in the description of the molecular mechanism underlying the resistance conferred by TgsGP. Notably it doesn't explain why TgsGP cannot confer resistance to T.b.brucei.

As was shown in the aforementioned paper, resistance to ApoL1 is principally mediated by the hydrophobic ß-sheet of the T. b. gambiense specific glycoprotein which induces stiffening of membranes upon interaction with lipids. However, other factors are involved in resistance, a change in the cysteine protease activity and TbHpHbR inactivation by a mutation. All those factors work together to confer resistance to T.b.gambiense and explain why expression of TgsGP is not sufficient to confer resistance to T.b.brucei.

Competing interests declared: I am a member of the lab that published the paper I cite above, although I was not involved in the work