Sandbox Reserved 1601: Difference between revisions
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===Mutations=== | ===Mutations=== | ||
There are a number of mutations that completely eliminate calcium uptake by the MCU. For example, mutation of W,D,E, or 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 which has a side chain constituting a primary contact point between TM1 and TM2.<ref name="Fan"/> Mutation of Phe326 or Gly331 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"/> | |||
==Medical Relevance== | ==Medical Relevance== | ||