Determination of the Membrane Topology of the Small EF-Hand Ca2 -Sensing Proteins CaBP7 and CaBP8Report as inadecuate




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The CaBPs represent a subfamily of small EF-hand containing calcium Ca2+-sensing proteins related to calmodulin that regulate key ion channels in the mammalian nervous system. In a recent bioinformatic analyses we determined that CaBP7 and CaBP8 form an evolutionarily distinct branch within the CaBPs also known as the calneurons a finding that is consistent with earlier observations characterising a putative C-terminal transmembrane TM spanning helix in each of these proteins which is essential for their sub-cellular targeting to the Golgi apparatus and constitutive secretory vesicles. The C-terminal position of the predicted TM-helix suggests that CaBP7 and CaBP8 could be processed in a manner analogous to tail-anchored integral membrane proteins which exhibit the ability to insert across membranes post-translationally. In this study we have investigated the topology of CaBP7 and CaBP8 within cellular membranes through a combination of trypsin protection and epitope accessibility analyses. Our results indicate that the TM-helices of CaBP7 and CaBP8 insert fully across membranes such that their extreme C-termini are luminal. The observed type-II membrane topology is consistent with processing of CaBP7 and CaBP8 as true tail-anchored proteins. This targeting mechanism is distinct from any other calmodulin related Ca2+-sensor and conceivably underpins unique physiological functions of these proteins.



Author: Hannah V. McCue, Robert D. Burgoyne, Lee P. Haynes

Source: http://plos.srce.hr/



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