User:Alice Harmon/Sandbox 2: Difference between revisions

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Crystal structures of inactive and active conformations of CDPK1 from ''Toxoplasma gondii'' show the dramatic conformation change that occurs upon the binding of calcium to the regulatory domain <ref> PMID:20436473 </ref>. See [[Eukaryotic Protein Kinase Catalytic Domain]] for a guide to their structure.  
Crystal structures of inactive and active conformations of CDPK1 from ''Toxoplasma gondii'' show the dramatic conformation change that occurs upon the binding of calcium to the regulatory domain <ref> PMID:20436473 </ref>. See [[Eukaryotic Protein Kinase Catalytic Domain]] for a guide to their structure.  


{|
{|
|'''Left scene''' - The crystal structure [[3ku2]] shows the '''inactive conformation''' of the kinase that is bound only to the ANP (wireframe and CPK coloring). As above, the catalytic domain is blue and the CAD is gold. The large lobe of the kinase domain is in approximately the same orientation as in the left scene. Note the large conformational change in the CAD (long alpha helices) and that it is now bound to the same side of the kinase as the catalytic cleft (marked by the bound ANP), blocking it from binding peptide substrate.
|'''Right scene''' - The crystal structure [[3hx4]] shows the '''active conformation''' of the kinase that is bound to calcium (green spheres) and the ATP analog ANP (also called AMPPNP; shown in wireframe and CPK coloring). The catalytic domain is blue and the calcium activation domain (CAD) is gold. In the kinase domain, ANP sits in the catalytic cleft between the large and small lobes of the domain. CAD is bound to the side of the kinase opposite to the catalytic cleft, making it available for peptide substrate binding.
|-
| <applet load='3ku2' size='400' frame='true' align='left' caption='3ku2 - inactive TgCDPK1' scene = '55/559103/Holo-ikinase/5' /><br>'''3ku2 scenes''' <Br><scene name='55/559103/Holo-ikinase_cad_rainbow/2'>1. Apo CAD</scene>shown in rainbow colors from the N-terminal (blue) to the C-terminal (red) ends of the domain. <br><scene name='55/559103/Holo-ikinase_cad_rainbow/3'>2. CAD helices</scene><br><scene name='55/559103/Holo-ikinase_cad_rainbow/4'>3. dummy</scene>
| <applet load='3HX4' size='400' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '55/559103/Holo-akinase/2' /><Br>'''3hx4 scenes'''<Br><scene name='55/559103/Holo-akinase_cad_rainbow/1'>1. Calcium-bound CAD</scene><br><scene name='55/559103/Holo-akinase_cad_rainbow/2'>2. CAD bent helices</scene><br><scene name='55/559103/Holo-akinase_cad_rainbow/3'>3. dummy</scene>
| <applet load='3HX4' size='400' frame='true' align='left' caption='3hx4 - active TgCDPK1' scene = '55/559103/Holo-akinase/2' /><Br>'''3hx4 scenes'''<Br><scene name='55/559103/Holo-akinase_cad_rainbow/1'>1. Calcium-bound CAD</scene><br><scene name='55/559103/Holo-akinase_cad_rainbow/2'>2. CAD bent helices</scene><br><scene name='55/559103/Holo-akinase_cad_rainbow/3'>3. dummy</scene>
| <applet load='3ku2' size='400' frame='true' align='left' caption='3ku2 - inactive TgCDPK1' scene = '55/559103/Holo-ikinase/5' /><br>'''3ku2 scenes''' <Br><scene name='55/559103/Holo-ikinase_cad_rainbow/2'>1. Apo CAD</scene><br><scene name='55/559103/Holo-ikinase_cad_rainbow/3'>2. CAD helices</scene><br><scene name='55/559103/Holo-ikinase_cad_rainbow/4'>3. dummy</scene>
|-
|The crystal structure [[3hx4]] in the left scene shows the '''active conformation''' of the kinase that is bound to calcium (green spheres) and the ATP analog ANP (also called AMPPNP; shown in wireframe and CPK coloring). The catalytic domain is blue and the calcium activation domain (CAD) is gold. In the kinase domain, ANP sits in the catalytic cleft between the large and small lobes of the domain. CAD is bound to the side of the kinase opposite to the catalytic cleft, making it available for peptide substrate binding.
|The crystal structure [[3ku2]] in the right scene shows the '''inactive conformation''' of the kinase that is bound only to the ANP (wireframe and CPK coloring). As above, the catalytic domain is blue and the CAD is gold. The large lobe of the kinase domain is in approximately the same orientation as in the left scene. Note the large conformational change in the CAD (long alpha helices) and that it is now bound to the same side of the kinase as the catalytic cleft (marked by the bound ANP), blocking it from binding peptide substrate.
|}
|}


Revision as of 15:24, 19 September 2013

CDPKCDPK

Calcium-dependent protein kinases (CDPKs) are found in plants, green algae, and protists. In plants CDPKs are encoded by large gene families[1][2] and they are involved in many cellular responses to stimuli such as hormones and environmental stress[3]. In the apicomplexan protists Plasmodium falciparum(parasite that causes malaria) and Toxoplasma gondii(parasite that causes toxoplasmosis), CDPKs are encoded by small gene families, and they are involved in critical stages of the parasite life cycle [4][5].

CDPKs are monomeric enzymes containing an amino-terminal protein kinase domain linked to a carboxy-terminal calcium-binding regulatory domain, which has sequence similarity to calmodulin, and they belong to the calmodulin-dependent protein kinase family[6]. CDPKs are regulated by the binding of calcium to the regulatory domain, and thus are activated in processes that elevate the concentration of calcium inside cells.

Crystal structures of inactive and active conformations of CDPK1 from Toxoplasma gondii show the dramatic conformation change that occurs upon the binding of calcium to the regulatory domain [7]. See Eukaryotic Protein Kinase Catalytic Domain for a guide to their structure.


Left scene - The crystal structure 3ku2 shows the inactive conformation of the kinase that is bound only to the ANP (wireframe and CPK coloring). As above, the catalytic domain is blue and the CAD is gold. The large lobe of the kinase domain is in approximately the same orientation as in the left scene. Note the large conformational change in the CAD (long alpha helices) and that it is now bound to the same side of the kinase as the catalytic cleft (marked by the bound ANP), blocking it from binding peptide substrate. Right scene - The crystal structure 3hx4 shows the active conformation of the kinase that is bound to calcium (green spheres) and the ATP analog ANP (also called AMPPNP; shown in wireframe and CPK coloring). The catalytic domain is blue and the calcium activation domain (CAD) is gold. In the kinase domain, ANP sits in the catalytic cleft between the large and small lobes of the domain. CAD is bound to the side of the kinase opposite to the catalytic cleft, making it available for peptide substrate binding.

3ku2 - inactive TgCDPK1

Drag the structure with the mouse to rotate

3ku2 scenes
shown in rainbow colors from the N-terminal (blue) to the C-terminal (red) ends of the domain.

3hx4 - active TgCDPK1

Drag the structure with the mouse to rotate

3hx4 scenes


ReferencesReferences

  1. ↑ Hrabak EM, Chan CW, Gribskov M, Harper JF, Choi JH, Halford N, Kudla J, Luan S, Nimmo HG, Sussman MR, Thomas M, Walker-Simmons K, Zhu JK, Harmon AC. The Arabidopsis CDPK-SnRK superfamily of protein kinases. Plant Physiol. 2003 Jun;132(2):666-80. PMID:12805596 doi:10.1104/pp.102.011999
  2. ↑ Asano T, Tanaka N, Yang G, Hayashi N, Komatsu S. Genome-wide identification of the rice calcium-dependent protein kinase and its closely related kinase gene families: comprehensive analysis of the CDPKs gene family in rice. Plant Cell Physiol. 2005 Feb;46(2):356-66. Epub 2005 Feb 2. PMID:15695435 doi:10.1093/pcp/pci035
  3. ↑ Schulz P, Herde M, Romeis T. Calcium-dependent protein kinases: hubs in plant stress signaling and development. Plant Physiol. 2013 Sep 6. PMID:24014579 doi:10.1104/pp.113.222539
  4. ↑ McCoy JM, Whitehead L, van Dooren GG, Tonkin CJ. TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells. PLoS Pathog. 2012;8(12):e1003066. doi: 10.1371/journal.ppat.1003066. Epub 2012, Dec 4. PMID:23226109 doi:10.1371/journal.ppat.1003066
  5. ↑ Dvorin JD, Martyn DC, Patel SD, Grimley JS, Collins CR, Hopp CS, Bright AT, Westenberger S, Winzeler E, Blackman MJ, Baker DA, Wandless TJ, Duraisingh MT. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science. 2010 May 14;328(5980):910-2. doi: 10.1126/science.1188191. PMID:20466936 doi:10.1126/science.1188191
  6. ↑ Harper JF, Sussman MR, Schaller GE, Putnam-Evans C, Charbonneau H, Harmon AC. A calcium-dependent protein kinase with a regulatory domain similar to calmodulin. Science. 1991 May 17;252(5008):951-4. PMID:1852075
  7. ↑ Wernimont AK, Artz JD, Finerty P Jr, Lin YH, Amani M, Allali-Hassani A, Senisterra G, Vedadi M, Tempel W, Mackenzie F, Chau I, Lourido S, Sibley LD, Hui R. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium. Nat Struct Mol Biol. 2010 May;17(5):596-601. Epub 2010 May 2. PMID:20436473 doi:10.1038/nsmb.1795

ReferencesReferences


ReferencesReferences

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