Abstract
The C-terminal GPI-attachment signal sequences (SSs) of proteins that receive GPI anchors need to be chopped off by the GPI-transamidase and replaced by preformed GPI precursor. The proteins and the anchors thereafter undergo several additional modifications before they are transported to their final destinations at the cell surface. Mutations in the SS that do not necessarily influence anchor attachment appear to still dictate the final fates of the proteins. How and why this happens is unclear though a couple of different hypotheses exist. Using the Als5 adhesin of C. albicans we propose another probable mechanism by which SSs could influence the destiny of the GPI anchored proteins. We had previously shown that the last 20-residues of SS, if left intact on the 1347-residue long protein, could interact with the amyloidogenic domain of Als5 and cause the otherwise natively unfolded Als5 to adopt a predominantly alpha helical conformation, reducing adhesion and preventing it from forming β-aggregates as is expected of the functional Als5. We had proposed that this was due to an interaction between the SS and the amyloidogenic domain on Als5. In this paper, we develop this theme further. We demonstrate that introducing mutations in the SS of Als5 appear to reduce the interactions between these domains and result in variants that resemble the mature protein in functionality. We propose that the actual conformations of the proprotein affects its interacting partners, thereby also influencing how the GPI anchored protein associates with ER exit sites.
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Acknowledgements
This work in SSK’s lab is supported in parts by funds from DST-PURSE grant to Jawaharlal Nehru University as well as UGC-Resource network grant to the School of Life Sciences. PGM receives a Senior Research Fellowship from UGC.
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Ahmad, M.F., Mann, P.G., Komath, S.S. (2015). A Signal with a Difference: The Role of GPI Anchor Signal Sequence in Dictating Conformation and Function of the Als5 Adhesin in Candida albicans. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_10
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