Sandbox Reserved 508: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Nikil Prasad (talk | contribs) No edit summary |
Nikil Prasad (talk | contribs) No edit summary |
||
| Line 5: | Line 5: | ||
== Abstract == | == Abstract == | ||
Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain.<ref name="Berardi">PMID:21785437</ref> Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification.<ref name="Krauss">PMID:15738989</ref> There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | ||
== Data Piece == | == Data Piece == | ||
[[Image:BCSMART_11-12_Figure_7.JPG|center|375px]] | [[Image:BCSMART_11-12_Figure_7.JPG|center|375px]] | ||
'''The Effect of UCP2 on ROS Production''' | '''The Effect of UCP2 on ROS Production''' | ||
<br> | <br> | ||
The data above shows the effect of UCP2 on ROS production. The ROS is made visible by DCF fluorescence(dichloro-fluorescein, which fluoresces in the presence of H2O2). ROS species are introduced into neonatal rat cardiac ventricular myocytes by injecting H2O2. | The data above .<ref name="Teshima">PMID: 12855674</ref> shows the effect of UCP2 on ROS production. The ROS is made visible by DCF fluorescence(dichloro-fluorescein, which fluoresces in the presence of H2O2). ROS species are introduced into neonatal rat cardiac ventricular myocytes by injecting H2O2. | ||
<br> | <br> | ||
A. Confocal microscope images of cardiomyocytes’ ROS production | A. Confocal microscope images of cardiomyocytes’ ROS production | ||
| Line 105: | Line 105: | ||
through the membrane by UCP2.]] | through the membrane by UCP2.]] | ||
<StructureSection load='2lck_pdb' scene='Sandbox_Reserved_508/2lck_pdb/12' size='750' side='middle' caption='Structure of UCP 2 displaying key features. In this model of UCP2, the light sea green parts represent the alpha helices which are thought to be involved in the transport of protons. All negatively-charged amino acids, glutamic and aspartic, are colored crimson. These may be involved in the direct transport of protons through UCP2. All positively charged amino acids, except for Lys141 and Arg185, are colored navy. These may be involved in the transport of deprotonated fatty acid molecules through UCP2, as well. Lys141 and Arg185, which are speculated to bind to the UCP2 inhibitor, GDP, are colored light sky blue. Helix sequences, conserved between different UCP proteins, which may also have a role in fatty acid transport, are colored orange. Helices found in the matrix or the inter-membrane space are colored light aquamarine. Loops, which are not involved in the active site, are colored white. '> | <StructureSection load='2lck_pdb' scene='Sandbox_Reserved_508/2lck_pdb/12' size='750' side='middle' caption='Uncoupling Protein 2, 2lck <ref name="Berardi">PMID:21785437</ref>Structure of UCP 2 displaying key features. In this model of UCP2, the light sea green parts represent the alpha helices which are thought to be involved in the transport of protons. All negatively-charged amino acids, glutamic and aspartic, are colored crimson. These may be involved in the direct transport of protons through UCP2. All positively charged amino acids, except for Lys141 and Arg185, are colored navy. These may be involved in the transport of deprotonated fatty acid molecules through UCP2, as well. Lys141 and Arg185, which are speculated to bind to the UCP2 inhibitor, GDP, are colored light sky blue. Helix sequences, conserved between different UCP proteins, which may also have a role in fatty acid transport, are colored orange. Helices found in the matrix or the inter-membrane space are colored light aquamarine. Loops, which are not involved in the active site, are colored white. '> | ||
==References== | ==References== | ||
<references /> | <references /> | ||
