Ricin: A toxic protein
From Proteopedia
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Ricin is a toxin protein found in castor beans and the seeds of the castor oil plant. This heterodimeric protein is produced as a part of the waste that comes from the production of castor oil. Ricin was discovered more than a century ago when the protein was isolated from seeds by Stillmark. The protein is considered toxic due to its observed ability to clump up red blood cells. Later studies showed that ricin was a mixture of the potent cytotoxin and hemagglutinin. Such mechanism of the ricin was discovered on 28S ribosomal RNA. Since then, several functionally related proteins have been discovered from different plants. Such proteins are referred to as ribosome-inactivating proteins due to their ability to irreversibly inactivate eukaryotic ribosomes and terminating protein synthesis. Certain types of ricin known as ‘type I Ricins’ have toxic characteristics however it is seen that they do not have the capability to enter cells in order to reach the ribosomes. Other types are known as ‘type II Ricin’ however, have the capability to enter the cells due to their differences in structures. | Ricin is a toxin protein found in castor beans and the seeds of the castor oil plant. This heterodimeric protein is produced as a part of the waste that comes from the production of castor oil. Ricin was discovered more than a century ago when the protein was isolated from seeds by Stillmark. The protein is considered toxic due to its observed ability to clump up red blood cells. Later studies showed that ricin was a mixture of the potent cytotoxin and hemagglutinin. Such mechanism of the ricin was discovered on 28S ribosomal RNA. Since then, several functionally related proteins have been discovered from different plants. Such proteins are referred to as ribosome-inactivating proteins due to their ability to irreversibly inactivate eukaryotic ribosomes and terminating protein synthesis. Certain types of ricin known as ‘type I Ricins’ have toxic characteristics however it is seen that they do not have the capability to enter cells in order to reach the ribosomes. Other types are known as ‘type II Ricin’ however, have the capability to enter the cells due to their differences in structures. | ||
===Structure=== | ===Structure=== | ||
| - | <scene name='88/882145/Ricin/4'>Type I Ricin</scene> only consists of the A-chain whereas <scene name='88/882145/Ricin/8'>Type II Ricin</scene> is comprised of the <scene name='88/882145/Ricin/7'>A-chain</scene> and the <scene name='88/882145/Ricin/5'>B-chain</scene> which are folded peptide chains, with the two chains linked by <scene name='88/882145/Ricin/ | + | <scene name='88/882145/Ricin/4'>Type I Ricin</scene> only consists of the A-chain whereas <scene name='88/882145/Ricin/8'>Type II Ricin</scene> is comprised of the <scene name='88/882145/Ricin/7'>A-chain</scene> and the <scene name='88/882145/Ricin/5'>B-chain</scene> which are folded peptide chains, with the two chains linked by <scene name='88/882145/Ricin/11'>disulfide bonds</scene>. Ricin has a molecular weight of 64-63 kDa, with the A-chain being 32 kDa and the B-chain being 36 kDa. The A-chain has the conformation of a globular protein domain with 267 amino acids consisting of 8 alpha-helices and 8 beta-sheets with the active site as a long cleft on its surface. The active site consists of a key catalytic residue Glutamic acid 177 which is deprotonated to glutamate reducing the activity immensely. Whereas the B-chain has the conformation of a barbell structure consisting of 26 amino acids, with a sugar-binding site at each end which allows it to hydrogen bond to galactose and N-acetyl galactosamine that is found on cell surfaces. The B-chain and the A-chain respectively do not cause the ricin to be toxic, Ricin’s toxicity is due to the presence of both chains because of their crucial roles together. The B-chain’s role is to acquire entry into eukaryotic cells, meanwhile, the A-chain is responsible for the toxicity because of its RNA N-glycosidase activity. Once the molecule enters the cell, the B-chain dissociates from the A-chain leaving it to exert its toxicity. |
<Structure load='1RTC' size='350' frame='true' align='right' caption='Type I Ricin' scene='Insert optional scene name here' /> | <Structure load='1RTC' size='350' frame='true' align='right' caption='Type I Ricin' scene='Insert optional scene name here' /> | ||
This is a default text for your page '''Ricin: A toxic protein'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | This is a default text for your page '''Ricin: A toxic protein'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | ||
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue. | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue. | ||
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| + | ===Biosynthesis=== | ||
| + | The inactive ricin precursor protein consists of 576 amino acid residues, a signal peptide known as the ricin A-chain and the linker peptide known as the ricin B-chain. The biosynthesis and activation of ricin precursor protein take place in the endosperm of castor oil seeds. The precursor protein is delivered to the endoplasmic reticulum with the help of the N-terminal signal sequence that gets cleaved off once the protein has been delivered. Once in the lumen of the endoplasmic reticulum, the precursor protein gets glycosylated, and a disulfide bond is formed between cysteines 294 and 318 with the help of protein disulfide isomerases causing the precursor protein chains to further fold into globular protein domains. The precursor protein is further glycosylated in the Golgi apparatus before it is transported to different protein bodies through storage vesicles. Once in the protein bodies, the ricin precursor protein is cleaved by an endopeptidase to finally give us the mature Ricin protein made up of a 267 residue A-chain and a 262 residue B-chain that are covalently linked by a disulfide bond. | ||
== Function == | == Function == | ||
Revision as of 02:36, 29 April 2021
Contents |
Background
Ricin is a toxin protein found in castor beans and the seeds of the castor oil plant. This heterodimeric protein is produced as a part of the waste that comes from the production of castor oil. Ricin was discovered more than a century ago when the protein was isolated from seeds by Stillmark. The protein is considered toxic due to its observed ability to clump up red blood cells. Later studies showed that ricin was a mixture of the potent cytotoxin and hemagglutinin. Such mechanism of the ricin was discovered on 28S ribosomal RNA. Since then, several functionally related proteins have been discovered from different plants. Such proteins are referred to as ribosome-inactivating proteins due to their ability to irreversibly inactivate eukaryotic ribosomes and terminating protein synthesis. Certain types of ricin known as ‘type I Ricins’ have toxic characteristics however it is seen that they do not have the capability to enter cells in order to reach the ribosomes. Other types are known as ‘type II Ricin’ however, have the capability to enter the cells due to their differences in structures.
Structure
only consists of the A-chain whereas is comprised of the and the which are folded peptide chains, with the two chains linked by . Ricin has a molecular weight of 64-63 kDa, with the A-chain being 32 kDa and the B-chain being 36 kDa. The A-chain has the conformation of a globular protein domain with 267 amino acids consisting of 8 alpha-helices and 8 beta-sheets with the active site as a long cleft on its surface. The active site consists of a key catalytic residue Glutamic acid 177 which is deprotonated to glutamate reducing the activity immensely. Whereas the B-chain has the conformation of a barbell structure consisting of 26 amino acids, with a sugar-binding site at each end which allows it to hydrogen bond to galactose and N-acetyl galactosamine that is found on cell surfaces. The B-chain and the A-chain respectively do not cause the ricin to be toxic, Ricin’s toxicity is due to the presence of both chains because of their crucial roles together. The B-chain’s role is to acquire entry into eukaryotic cells, meanwhile, the A-chain is responsible for the toxicity because of its RNA N-glycosidase activity. Once the molecule enters the cell, the B-chain dissociates from the A-chain leaving it to exert its toxicity.
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This is a default text for your page Ricin: A toxic protein. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Biosynthesis
The inactive ricin precursor protein consists of 576 amino acid residues, a signal peptide known as the ricin A-chain and the linker peptide known as the ricin B-chain. The biosynthesis and activation of ricin precursor protein take place in the endosperm of castor oil seeds. The precursor protein is delivered to the endoplasmic reticulum with the help of the N-terminal signal sequence that gets cleaved off once the protein has been delivered. Once in the lumen of the endoplasmic reticulum, the precursor protein gets glycosylated, and a disulfide bond is formed between cysteines 294 and 318 with the help of protein disulfide isomerases causing the precursor protein chains to further fold into globular protein domains. The precursor protein is further glycosylated in the Golgi apparatus before it is transported to different protein bodies through storage vesicles. Once in the protein bodies, the ricin precursor protein is cleaved by an endopeptidase to finally give us the mature Ricin protein made up of a 267 residue A-chain and a 262 residue B-chain that are covalently linked by a disulfide bond.
Function
Disease
Relevance
Structural highlights
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
</StructureSection>
References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
