User:Alice Harmon/EF Hand: Difference between revisions

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EF-~~hands are~~ calcium-binding ~~motifs~~ found in hundreds of proteins. They bind calcium ions with high affinity (Kds are in the micromolar range) and selectivity, and this property allows EF-hand proteins to sense changes in intracellular calcium. In unstimulated cells cellular free calcium concentrations [Ca2+]c are in the nanomolar range (~10 nM in animal cells and ~200 nM in plant cells), and EF-hands are generally unoccupied by Ca2+. Upon stimulation, Ca2+ enters the cytosol from either outside the cell or from internal organelles, and [Ca2+]c rises to the micromolar range. EF-hands bind Ca2+, and this binding causes a conformational change that alters the activity of the protein.

The EF-hand is a calcium-binding motif found in hundreds of proteins. They bind calcium ions with high affinity (Kds are in the micromolar range) and selectivity, and this property allows EF-hand proteins to sense changes in intracellular calcium. In unstimulated cells cellular free calcium concentrations [Ca2+]c are in the nanomolar range (~10 nM in animal cells and ~200 nM in plant cells), and EF-hands are generally unoccupied by Ca2+. Upon stimulation, Ca2+ enters the cytosol from either outside the cell or from internal organelles, and [Ca2+]c rises to the micromolar range. EF-hands bind Ca2+, and this binding causes a conformational change that alters the activity of the protein.

This page focuses on the structure of EF hands. For additional information see http://en.wikipedia.org/wiki/EF_hand.

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The calcium ion is coordinated by seven oxygen atoms that form a pentagonal bipyramid (five atoms form the base of the pyramid and the other two the points). One oxygen is contributed by each of the side chains of residues in positions 1, 3, 5, 9; two are from the side chain of E or D at position 12; one is from the backbone of the residue at position 7; and one from water.

Below are three examples of EF-hand proteins. [[parvalbumin]] has a pair of EF-hands, [[calmodulin]] ~~has~~ two pair, and [[calcium-dependent protein kinase]]~~, has two pair in its calcium-binding domain that~~ is ~~attached to~~ a protein kinase catalytic domain. As shown in these examples EF-hands often occur in pairs, which enables the cooperative binding of calcium ions. The initial scene shows the proteins in cartoon with Ca2+ in green space fill. The calcium binding domain of CDPK is blue and the kinase catalytic domain is in gold and has an ATP analog (sticks in CPK colors) bound in its active site.

Below are three examples of EF-hand proteins. [[parvalbumin]] is a monomeric protein that has a pair of EF-hands, [[calmodulin]] is a monomer with two pair, and [[calcium-dependent protein kinase]] is a monomer with a protein kinase catalytic domain (gold) and calcium-binding domain (blue) that has two pair of EF hands. As shown in these examples EF-hands often occur in pairs, which enables the cooperative binding of calcium ions. The initial scene shows the proteins in cartoon with Ca2+ in green space fill. The calcium binding domain of CDPK is blue and the kinase catalytic domain is in gold and has an ATP analog (sticks in CPK colors) bound in its active site.

Scenes numbered 1 show pairs of EF-hands in each protein, one in blue and one in gold, which are linked by the sequence shown in orchid.

Scenes numbered 2 isolate one E-F hand: the eponymous E-F hand of parvalbumen, E-F hand I (they are numbered I-IV) in calmodulin, and E-F hand IV of CDPK.

Scenes numbered 2 isolate one EF-hand: the eponymous EF-hand of parvalbumen, EF-hand I (they are numbered I-IV) in calmodulin, and EF-hand IV of CDPK.

Scenes numbered 3 show the calcium binding loops, which are shown in the same orientation. The five residues that contribute oxygens form the base of pyramid are distributed around the equator of the calcium ion, the "north" pyramid point is the oxygen from water, and the "south" point is the invariant D at position 1 in the motif.

{|

| <applet load='4cpv' size='300' frame='true' align='right' caption='4cpv - Carp parvalbumin' scene='56/562354/Parvalbumin/1' /> '''4cpv''' <scene name='56/562354/Parvalbumin/2'>1. Pair of EF-hands</scene> <scene name='56/562354/Parvalbumin/3'>2. The original E-F Hand</scene> <scene name='56/562354/Parvalbumin/6'>3. Calcium binding ~~ligands~~</scene>

| <applet load='4cpv' size='300' frame='true' align='right' caption='4cpv - Carp parvalbumin' scene='56/562354/Parvalbumin/1' /> '''4cpv''' <scene name='56/562354/Parvalbumin/2'>1. Pair of EF-hands</scene> <scene name='56/562354/Parvalbumin/3'>2. The original EF-Hand</scene> <scene name='56/562354/Parvalbumin/6'>3. Calcium-binding loop</scene>

| <applet load='1prw' size='300' frame='true' align='right' caption='1prw - Bovine calmodulin' scene='56/562354/Calmodulin/1' /> '''1prw''' <scene name='56/562354/Calmodulin/3'>1. Pair of EF hands</scene> <scene name='56/562354/Calmodulin/4'>2. EF hand I</scene> <scene name='56/562354/Calmodulin/7'>3. Ca-binding ~~ligands~~</scene>

| <applet load='1prw' size='300' frame='true' align='right' caption='1prw - Bovine calmodulin' scene='56/562354/Calmodulin/1' /> '''1prw''' <scene name='56/562354/Calmodulin/3'>1. Pair of EF-hands</scene> <scene name='56/562354/Calmodulin/4'>2. EF-hand I</scene> <scene name='56/562354/Calmodulin/7'>3. Calcium-binding loop</scene>

| <applet load='3HX4' size='300' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '56/562354/Cdpk/1' /> '''3HX4''' <scene name='56/562354/Cdpk_ef_hand_pair/2'>1. Pair of EF hands</scene> <scene name='56/562354/Cdpk_ef_iv/1'>2. EF ~~Hand~~ IV</scene> <scene name='56/562354/Cdpk_ef_iv/3'>3. Calcium-binding ~~ligands~~</scene>

| <applet load='3HX4' size='300' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '56/562354/Cdpk/1' /> '''3HX4''' <scene name='56/562354/Cdpk_ef_hand_pair/2'>1. Pair of EF-hands</scene> <scene name='56/562354/Cdpk_ef_iv/1'>2. EF-hand IV</scene> <scene name='56/562354/Cdpk_ef_iv/3'>3. Calcium-binding loop</scene>

|}

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-EF-hands are calcium-binding motifs found in hundreds of proteins. They bind calcium ions with high affinity (K<sub>d</sub>s are in the micromolar range) and selectivity, and this property allows EF-hand proteins to sense changes in intracellular calcium. In unstimulated cells cellular free calcium concentrations [Ca<sup>2+</sup>]<sub>c</sub> are in the nanomolar range (~10 nM in animal cells and ~200 nM in plant cells), and EF-hands are generally unoccupied by Ca<sup>2+</sup>. Upon stimulation, Ca<sup>2+</sup> enters the cytosol from either outside the cell or from internal organelles, and [Ca<sup>2+</sup>]<sub>c</sub> rises to the micromolar range. EF-hands bind Ca<sup>2+</sup>, and this binding causes a conformational change that alters the activity of the protein.
+The EF-hand is a calcium-binding motif found in hundreds of proteins. They bind calcium ions with high affinity (K<sub>d</sub>s are in the micromolar range) and selectivity, and this property allows EF-hand proteins to sense changes in intracellular calcium. In unstimulated cells cellular free calcium concentrations [Ca<sup>2+</sup>]<sub>c</sub> are in the nanomolar range (~10 nM in animal cells and ~200 nM in plant cells), and EF-hands are generally unoccupied by Ca<sup>2+</sup>. Upon stimulation, Ca<sup>2+</sup> enters the cytosol from either outside the cell or from internal organelles, and [Ca<sup>2+</sup>]<sub>c</sub> rises to the micromolar range. EF-hands bind Ca<sup>2+</sup>, and this binding causes a conformational change that alters the activity of the protein.
 This page focuses on the structure of EF hands. For additional information see http://en.wikipedia.org/wiki/EF_hand.
@@ Line 18: / Line 18: @@
 The calcium ion is coordinated by seven oxygen atoms that form a pentagonal bipyramid (five atoms form the base of the pyramid and the other two the points). One oxygen is contributed by each of the side chains of residues in positions 1, 3, 5, 9; two are from the side chain of E or D at position 12; one is from the backbone of the residue at position 7; and one from water.
-Below are three examples of EF-hand proteins. [[parvalbumin]] has a pair of EF-hands, [[calmodulin]] has two pair, and [[calcium-dependent protein kinase]], has two pair in its calcium-binding domain that is attached to a protein kinase catalytic domain. As shown in these examples EF-hands often occur in pairs, which enables the cooperative binding of calcium ions. The initial scene shows the proteins in cartoon with Ca2+ in green space fill. The calcium binding domain of CDPK is blue and the kinase catalytic domain is in gold and has an ATP analog (sticks in CPK colors) bound in its active site.
+Below are three examples of EF-hand proteins. [[parvalbumin]] is a monomeric protein that has a pair of EF-hands, [[calmodulin]] is a monomer with two pair, and [[calcium-dependent protein kinase]] is a monomer with a protein kinase catalytic domain (gold) and calcium-binding domain (blue) that has two pair of EF hands. As shown in these examples EF-hands often occur in pairs, which enables the cooperative binding of calcium ions. The initial scene shows the proteins in cartoon with Ca2+ in green space fill. The calcium binding domain of CDPK is blue and the kinase catalytic domain is in gold and has an ATP analog (sticks in CPK colors) bound in its active site.
 Scenes numbered 1 show pairs of EF-hands in each protein, one in blue and one in gold, which are linked by the sequence shown in orchid.<br>
-Scenes numbered 2 isolate one E-F hand: the eponymous E-F hand of parvalbumen, E-F hand I (they are numbered I-IV) in calmodulin, and E-F hand IV of CDPK.<br>
+Scenes numbered 2 isolate one EF-hand: the eponymous EF-hand of parvalbumen, EF-hand I (they are numbered I-IV) in calmodulin, and EF-hand IV of CDPK.<br>
 Scenes numbered 3 show the calcium binding loops, which are shown in the same orientation. The five residues that contribute oxygens form the base of pyramid are distributed around the equator of the calcium ion, the "north" pyramid point is the oxygen from water, and the "south" point is the invariant D at position 1 in the motif.
 {|
-| <applet load='4cpv' size='300' frame='true' align='right' caption='4cpv - Carp parvalbumin' scene='56/562354/Parvalbumin/1' /><Br>'''4cpv''' <Br><scene name='56/562354/Parvalbumin/2'>1. Pair of EF-hands</scene><br><scene name='56/562354/Parvalbumin/3'>2. The original E-F Hand</scene><br><scene name='56/562354/Parvalbumin/6'>3. Calcium binding ligands</scene>
+| <applet load='4cpv' size='300' frame='true' align='right' caption='4cpv - Carp parvalbumin' scene='56/562354/Parvalbumin/1' /><Br>'''4cpv''' <Br><scene name='56/562354/Parvalbumin/2'>1. Pair of EF-hands</scene><br><scene name='56/562354/Parvalbumin/3'>2. The original EF-Hand</scene><br><scene name='56/562354/Parvalbumin/6'>3. Calcium-binding loop</scene>
-| <applet load='1prw' size='300' frame='true' align='right' caption='1prw - Bovine calmodulin' scene='56/562354/Calmodulin/1' /><Br>'''1prw''' <Br><scene name='56/562354/Calmodulin/3'>1. Pair of EF hands</scene><br><scene name='56/562354/Calmodulin/4'>2. EF hand I</scene><br><scene name='56/562354/Calmodulin/7'>3. Ca-binding ligands</scene>
+| <applet load='1prw' size='300' frame='true' align='right' caption='1prw - Bovine calmodulin' scene='56/562354/Calmodulin/1' /><Br>'''1prw''' <Br><scene name='56/562354/Calmodulin/3'>1. Pair of EF-hands</scene><br><scene name='56/562354/Calmodulin/4'>2. EF-hand I</scene><br><scene name='56/562354/Calmodulin/7'>3. Calcium-binding loop</scene>
-| <applet load='3HX4' size='300' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '56/562354/Cdpk/1' /><Br>'''3HX4'''<Br><scene name='56/562354/Cdpk_ef_hand_pair/2'>1. Pair of EF hands</scene><br><scene name='56/562354/Cdpk_ef_iv/1'>2. EF Hand IV</scene><br><scene name='56/562354/Cdpk_ef_iv/3'>3. Calcium-binding ligands</scene>
+| <applet load='3HX4' size='300' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '56/562354/Cdpk/1' /><Br>'''3HX4'''<Br><scene name='56/562354/Cdpk_ef_hand_pair/2'>1. Pair of EF-hands</scene><br><scene name='56/562354/Cdpk_ef_iv/1'>2. EF-hand IV</scene><br><scene name='56/562354/Cdpk_ef_iv/3'>3. Calcium-binding loop</scene>
 |}