Sandbox Reserved 1626: Difference between revisions

There are a number of mutations that completely eliminate calcium uptake by the MCU.  For example, mutation of [https://en.wikipedia.org/wiki/Tryptophan W], [https://en.wikipedia.org/wiki/Aspartic_acid D], [https://en.wikipedia.org/wiki/Glutamic_acid E], or [https://en.wikipedia.org/wiki/Proline P] of the WDXXEP motif altered the highly conserved selectivity filter and completely eliminated calcium uptake.<ref name="Baradaran"/><ref name="Fan"/>  For example, even mutating Glu228 to an aspartate significantly changed the dimensions of the pore and inhibited uptake of calcium.<ref name="Baradaran"/> However, mutation of either X residue was not detrimental to calcium uptake.<ref name="Baradaran"/> Furthermore, mutation of a tyrosine residue directly below the selectivity filter substantially impaired calcium intake and proper protein folding.<ref name="Fan"/> The residue on TM1 that affected calcium uptake the most in human MCU was Trp317 (<scene name='83/832952/New_ones/7'>Trp210</scene>) which has a side chain constituting a primary contact point between TM1 and TM2.<ref name="Fan"/> Mutation of Phe326 (<scene name='83/832952/New_ones/8'>Phe218</scene>) or '''Gly331 (Gly223)''' of the TM1-TM2 linker in human MCU affected the linker conformation and configuration of the pore entrance and impaired calcium intake.<ref name="Fan"/>