User:Christopher French: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 6: | Line 6: | ||
Caspase 8 is a member of the caspase family, a family of cysteine proteases that play an important role in inflammation and apoptosis | Caspase 8 is a member of the caspase family, a family of cysteine proteases that play an important role in inflammation and apoptosis (programmed cell death). The caspases are essential for apoptosis in cells during development and during later stages of life. Failure of apoptosis can lead to tumor formation and the development of autoimmune diseases. In addition, excess apoptosis has been implicated in various disease states, including ischemia and Alzheimer’s. Caspase 8 is just one of 11 caspases that have been indentified in humans. Caspase 8 is an “initiator caspase” which cleave inactive pro-forms of the effector caspases which activates them. Caspases exist as inactive proenzymes that are composed of a prodomain, and a large and small protease subunit. The activation of caspase requires proteolysis at an internal aspartic residue which results in the generation of a heterodimeric enzyme with a large and small subunit. [[Image:Apoptosiscascade.jpg]] (1). | ||
Caspase 8 is induced by tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). TRAIL induces apoptosis via death receptors (DR4 and DR5). After ligand binding the death receptor Fas recruits the adaptor protein FADD. FADD then binds and activates procaspase-8. Upon activation, Caspase 8 is then able activate caspase 3 and other downstream effectors. The end result is apoptosis (2,3) | Caspase 8 is induced by tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). TRAIL induces apoptosis via death receptors (DR4 and DR5). After ligand binding the death receptor Fas recruits the adaptor protein FADD. FADD then binds and activates procaspase-8. Upon activation, Caspase 8 is then able activate caspase 3 and other downstream effectors. The end result is apoptosis (2,3). | ||
| Line 17: | Line 17: | ||
Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as p18 and p11. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side. There is a turn of helix (α1’) which is part of a large loop (loop 1). This is along the binding pocket region of the p18 subunit. There is a two-stranded antiparallel ß sheet found at the top of the main ß sheet which forms the base of the binding pocket (4,5). | Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as p18 and p11. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side, forming a 3-layer bata sandwich. The p18 subunit has a Rossmann fold. There is a turn of helix (α1’) which is part of a large loop (loop 1). This is along the binding pocket region of the p18 subunit. There is a two-stranded antiparallel ß sheet found at the top of the main ß sheet which forms the base of the binding pocket (4,5). | ||
{{STRUCTURE_1qtn | PDB=1qtn | SCENE= }}<scene name='User:Christopher_French/Secondary_structure/3'>see secondary structure</scene><scene name='User:Christopher_French/Subunits/1'>subunits</scene> | {{STRUCTURE_1qtn | PDB=1qtn | SCENE= }}<scene name='User:Christopher_French/Secondary_structure/3'>see secondary structure</scene><scene name='User:Christopher_French/Subunits/1'>subunits</scene> | ||
<scene name='User:Christopher_French/Turn_of_helix/2'>see turn of helix</scene> | <scene name='User:Christopher_French/Turn_of_helix/2'>see turn of helix</scene> | ||
| Line 28: | Line 27: | ||
'''Heterotetramer''' | '''Heterotetramer''' | ||
Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. Residues Lys367-Asp374 of one heterodimer extends into the other heterodimer and interact with residues Thr390 and Asp395(4). | Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. Residues Lys367-Asp374 of one heterodimer extends into the other heterodimer and interact with residues Thr390 and Asp395(4). <scene name='User:Christopher_French/Heterotetramer/1'>see heterotetramer linkers</scene> | ||
