Sandbox Reserved 1626: Difference between revisions
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[[Image:Electronegativity_MCU_4.jpg|200 px|right|thumb|'''Fig. 1''' Electronegativity of the MCU viewed from outside the mouth of the channel. The high concentration of negative charge (shown in red) attracts the positive character of calcium ions. Created using PyMOL.]] | [[Image:Electronegativity_MCU_4.jpg|200 px|right|thumb|'''Fig. 1''' Electronegativity of the MCU viewed from outside the mouth of the channel. The high concentration of negative charge (shown in red) attracts the positive character of calcium ions. Created using PyMOL.]] | ||
The <scene name='83/832952/Selectivity_filter/3'>selectivity filter</scene> of the MCU is composed by many acidic amino acids near the narrow mouth of the channel which leads to high affinity for calcium ([https://en.wikipedia.org/wiki/Dissociation_constant dissociation constant] of less than 2nM).<ref name="Baradaran"/> The arrangement of the highly conserved <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> [https://en.wikipedia.org/wiki/Sequence_motif motif] in the TM2 helices form a ring in the pore to which calcium ions are attracted.<ref name="Baradaran"/> The structure in the animation is the MCU of [http://www.mycobank.org/BioloMICS.aspx?Table=Mycobank&Rec=511257 ''Cyphellophora europaea''] so every amino acid named here specifically is that of ''C. europaea'', but most of these residues are highly conserved across all species, though residue number may change. Though not part of the <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> motif, '''Asp221''' is present at the mouth of the MCU and serves to congregate positively charged <scene name='83/832952/Calcium/4'>calcium ions</scene> at the entrance of the channel.<ref name="Baradaran"/> The <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> motif consists of <scene name='83/832952/Tryptophan/2'>Trp224</scene> at the N-terminal end, <scene name='83/832952/Selectivity_filter_asp/2'>Asp225</scene>, <scene name='83/832952/Selectivity_filter_glu/3'>Glu228</scene>, and Pro229.<ref name="Baradaran"/> <scene name='83/832952/Tryptophan_proline/2'> | The <scene name='83/832952/Selectivity_filter/3'>selectivity filter</scene> of the MCU is composed by many acidic amino acids near the narrow mouth of the channel which leads to high affinity for calcium ([https://en.wikipedia.org/wiki/Dissociation_constant dissociation constant] of less than 2nM).<ref name="Baradaran"/> The arrangement of the highly conserved <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> [https://en.wikipedia.org/wiki/Sequence_motif motif] in the TM2 helices form a ring in the pore to which calcium ions are attracted.<ref name="Baradaran"/> The structure in the animation is the MCU of [http://www.mycobank.org/BioloMICS.aspx?Table=Mycobank&Rec=511257 ''Cyphellophora europaea''] so every amino acid named here specifically is that of ''C. europaea'', but most of these residues are highly conserved across all species, though residue number may change. Though not part of the <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> motif, '''Asp221''' is present at the mouth of the MCU and serves to congregate positively charged <scene name='83/832952/Calcium/4'>calcium ions</scene> at the entrance of the channel.<ref name="Baradaran"/> The <scene name='83/832952/Dxxe_motif/7'>WDXXEP</scene> motif consists of <scene name='83/832952/Tryptophan/2'>Trp224</scene> at the N-terminal end, <scene name='83/832952/Selectivity_filter_asp/2'>Asp225</scene>, <scene name='83/832952/Selectivity_filter_glu/3'>Glu228</scene>, and '''Pro229'''.<ref name="Baradaran"/> <scene name='83/832952/Tryptophan_proline/2'>Trp224 and Pro229</scene> pack against each other and are oriented towards the pore, but only serve to stabilize <scene name='83/832952/Selectivity_filter_glu/4'>Asp225 and Glu228</scene>, not interact with calcium ions.<ref name="Baradaran"/><ref name="Fan"/> The X residues ('''Val226''' and '''Met227''' in this case) face away from the pore and are exposed to the membrane.<ref name="Baradaran"/> The negatively charged side chains of Asp225 and Glu228 point towards the pore and form rings of radius 2.5Å and 1Å, respectively.<ref name="Baradaran"/> It's a combination of these radii and charges that account for the selectivity of the MCU. For example, potassium has an [https://en.wikipedia.org/wiki/Ionic_radius ionic radius] of 1.38Å which is much larger than the 1.00Å ionic radius of calcium.<ref name="Baradaran"/> Additionally, even though sodium ions have a similar ionic radius, the +2 charge on calcium is better matched to coordination with the glutamate residues.<ref name="Baradaran"/> | ||
===Movement of Calcium=== | ===Movement of Calcium=== | ||
