User:Laurine Seltz/Sandbox 1
From Proteopedia
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| - | + | '''Gemin5 pre-snRNA''' <ref>PMID:27834343</ref> | |
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| - | + | During the phenomenon of [https://en.wikipedia.org/wiki/RNA_splicing splicing] and the assembly of the [https://en.wikipedia.org/wiki/Exon exons] in the eukaryotes cells, there are some important complexes that are needed: the [https://en.wikipedia.org/wiki/Spliceosome spliceosomes] which are formed of [https://en.wikipedia.org/wiki/SnRNP snRNP] (small nuclear ribonucleoprotein particles). These particles are produced due to interaction between the Sm core protein and some small nuclear RNA, regulated by the complex of the survival of motor neurons that works as a [https://en.wikipedia.org/wiki/Chaperone_(protein) chaperone]. This last complex is composed of three proteins, the SMN, [http://www.uniprot.org/uniprot/Q8TEQ6 Unrip] and the proteins Gemin2 to Gemin8. | |
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| - | == | + | <Structure load='5h3u' size='350' frame='true' align='right' caption='3D Structure Gemin5 and pre-snRNA' scene='Insert optional scene name here' /> |
| - | During the phenomenon of splicing and the assembly of the exons in the eukaryotes cells, there are some important complexes that are needed: the [https://en.wikipedia.org/wiki/Spliceosome spliceosomes] which are formed of snRNPs (small nuclear ribonucleoprotein particles). These particles are produced due to interaction between the Sm core protein and some small nuclear RNA, regulated by the complex of the survival of motor neurons that works as a chaperone. This last complex is composed of three proteins, the SMN, Unrip and the proteins Gemin2 to Gemin8. | ||
== Function == | == Function == | ||
| - | Gemin5 | + | Gemin5 regulates the specificity that chooses the snRNA precursors and makes the transition to the Sm proteins. In others words, it helps to generate the spliceosome complex. |
| - | The specificity of Gemin5 is due to two | + | The [https://en.wikipedia.org/wiki/Chemical_specificity specificity] of [http://www.uniprot.org/uniprot/Q9Y3F4 Gemin5] is due to two bindings on different sequences on the Sm core protein. |
== Structure == | == Structure == | ||
| - | The apo form of Gemin5 shows 14 WD motifs able to fold into 2 connected seven-bladed β-propellers. The first doughnut-shaped propeller is called WD1 and is composed of blades 1 to 7 corresponding to the amino acids 19 to 377. The second is called WD2, composed of blades 8 to 14 corresponding to the amino acids 428 to 712. They are very similar in size, with around 38 Å in diameter, around 55 Å high and twisted around 15° askew relative to one another. The N-terminal region of WD1 forms the outermost β-strand of blade 14 in WD2. This structural motif is said to be referred to a “molecular | + | The apo form of Gemin5 shows that 14 WD motifs are able to fold into 2 connected seven-bladed [https://en.wikipedia.org/wiki/Beta-propeller β-propellers]. The first doughnut-shaped propeller is called <scene name='75/750246/Wd1/1'>WD1</scene> and is composed of blades 1 to 7 corresponding to the amino acids 19 to 377. The second is called <scene name='75/750246/Wd2/1'>WD2</scene>, composed of blades 8 to 14 corresponding to the amino acids 428 to 712. They are very similar in size, with around 38 Å in diameter, around 55 Å high and twisted around 15° askew relative to one another. The N-terminal region of <scene name='75/750246/Wd1/1'>WD1</scene> forms the outermost β-strand of blade 14 in <scene name='75/750246/Wd2/1'>WD2</scene>. This structural motif is said to be referred to a “molecular [https://en.wikipedia.org/wiki/Hook_and_loop_fastener velcro]”, also found in the structure of Aip1. |
---- | ---- | ||
| - | The WD-40 motif is also known as WD or beta-transducin. It is a short motif which contains around 40 amino acids and often ended with the Trp-Asp, or W-D, amino acids. Most of the time, WD-40 motifs folded into a 7-8 bladed beta-propeller. Proteins containing WD motifs exist in all eukaryotes and have different functions. Repeated WD-40 motifs are a site for protein-protein interactions and it had been shown that they act as platforms for the assembly of protein complexes. The specificity of the recognition is based on the sequences outside the repeats. Here are some examples of proteins which contains such a motif : E3 ubiquitin ligase [(PUBMED:11814058), (PUBMED:10322433)], TAFII transcription factor, beta subunit of G proteins. | + | The WD-40 [https://en.wikipedia.org/wiki/Structural_motif motif] is also known as WD or beta-transducin. It is a short motif which contains around 40 amino acids and often ended with the Trp-Asp, or W-D, amino acids. Most of the time, WD-40 motifs folded into a 7-8 bladed beta-propeller. Proteins containing WD motifs exist in all eukaryotes and have different functions. Repeated WD-40 motifs are a site for protein-protein interactions and it had been shown that they act as platforms for the assembly of protein complexes. The specificity of the recognition is based on the sequences outside the repeats. Here are some examples of proteins which contains such a motif : E3 ubiquitin ligase [(PUBMED:11814058), (PUBMED:10322433)], TAFII transcription factor, beta subunit of G proteins. |
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== Interactions == | == Interactions == | ||
| - | The way of working of the protein is based on a lot of interactions. For instance | + | The way of working of the protein is based on a lot of interactions. For instance the SmRNA with <scene name='75/750246/Wd1/1'>WD1</scene> and <scene name='75/750246/Wd2/1'>WD2</scene>. Indeed the blade 14 is linked to the 3’side of the SmRNA and it makes a lot of interactions with <scene name='75/750246/Wd1/1'>WD1</scene>. On the other side, which is the 5’ side of the SmRNA, we find the blade 8 that contains Trip 422 and EWD2. Moreover it contains <scene name='75/750246/Trp14/1'>Trp14</scene> which directly stacks against [https://fr.wikipedia.org/wiki/ARNsn_U5 U5], which stacks itself against [https://fr.wikipedia.org/wiki/ARNsn_U6 U6] . <scene name='75/750246/Arg359/1'>Arg359</scene>, <scene name='75/750246/Arg33/1'>Arg33</scene> and Asm 13 also stack against U6. Asm recognizes a base of U6. On the same model, the terminal nucleobase of U7 stacks against <scene name='75/750246/Phe382/1'>Phe382</scene> and WD40 domain of DDB2 recognizes dsDNA. Trp286 is located in a hydrophobic core of blade of <scene name='75/750246/Wd1/1'>WD1</scene>, contacting Tyr15 which stacks against the flipped nucleotide of U6. |
| + | SmRNA is recognized through 2 grooves formed on either side of Tyr15 in <scene name='75/750246/Wd1/1'>WD1</scene> and Tyr15 stacks against a flipped nucleotide of [https://fr.wikipedia.org/wiki/ARNsn_U4 U4] . Moreover, 5’side is linked to blades 7 and 8, that helds nucleotides U3 and A2. Indeed A2 and U3 are attached by hydrogen bonds because of the guanidinium group of Arg333 which is between A2 and [https://en.wikipedia.org/wiki/Small_nucleolar_RNA_U3 U3]. They stack against each other as well as A1. | ||
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| + | To further characterize the role of residues involved in SmRNA binding we mutated several conserved residues in Gemin5-WD, wich allowed us to get these results. It shows a real connection between all thoses parts. | ||
== Disease == | == Disease == | ||
| - | The SMN plays an important role and its deficiency can tend to a degenerative disease linked | + | The SMN plays an important role and its deficiency can tend to a degenerative disease linked to the motor neurons. It is called the SMA (spinal muscular atrophy) and made a disfunction in the expression of SMN1 that codes for the synthesis of the protein of the SMN complex. It is the second common recessive disease after cystic fibrosis. The death of neurons causes a paralysis of some members and weaknesses in every muscle of the body. The disease can occur four different ways: |
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| - | + | - Type I: it is the most extreme form of the disease that is diagnosed at birth. The patient has no hope of living, life expectancy: 2 years. The ill child is not able to sit or to walk. | |
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| + | - Type II: it is possible to detect it since the age of 6 months. It is characterized by an incapacity to independently walk but a capacity to sit. | ||
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| + | - Type III: it is the last juvenile form. There are less consequences than in the two other forms, ill people can do both activities without any help. | ||
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| + | - Type IV: it only affects adults and the conséquences are a weakness of the different muscles due to [https://en.m.wikipedia.org/wiki/Hypotonia hypotonia]. | ||
| + | <ref>PMID:19343312</ref> | ||
| + | <ref>PMID:7813012</ref> | ||
| - | == Structural highlights == | ||
| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> 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 == | == References == | ||
| + | |||
<references/> | <references/> | ||
Current revision
Gemin5 pre-snRNA [1]
During the phenomenon of splicing and the assembly of the exons in the eukaryotes cells, there are some important complexes that are needed: the spliceosomes which are formed of snRNP (small nuclear ribonucleoprotein particles). These particles are produced due to interaction between the Sm core protein and some small nuclear RNA, regulated by the complex of the survival of motor neurons that works as a chaperone. This last complex is composed of three proteins, the SMN, Unrip and the proteins Gemin2 to Gemin8.
|
Contents |
Function
Gemin5 regulates the specificity that chooses the snRNA precursors and makes the transition to the Sm proteins. In others words, it helps to generate the spliceosome complex. The specificity of Gemin5 is due to two bindings on different sequences on the Sm core protein.
Structure
The apo form of Gemin5 shows that 14 WD motifs are able to fold into 2 connected seven-bladed β-propellers. The first doughnut-shaped propeller is called and is composed of blades 1 to 7 corresponding to the amino acids 19 to 377. The second is called , composed of blades 8 to 14 corresponding to the amino acids 428 to 712. They are very similar in size, with around 38 Å in diameter, around 55 Å high and twisted around 15° askew relative to one another. The N-terminal region of forms the outermost β-strand of blade 14 in . This structural motif is said to be referred to a “molecular velcro”, also found in the structure of Aip1.
The WD-40 motif is also known as WD or beta-transducin. It is a short motif which contains around 40 amino acids and often ended with the Trp-Asp, or W-D, amino acids. Most of the time, WD-40 motifs folded into a 7-8 bladed beta-propeller. Proteins containing WD motifs exist in all eukaryotes and have different functions. Repeated WD-40 motifs are a site for protein-protein interactions and it had been shown that they act as platforms for the assembly of protein complexes. The specificity of the recognition is based on the sequences outside the repeats. Here are some examples of proteins which contains such a motif : E3 ubiquitin ligase [(PUBMED:11814058), (PUBMED:10322433)], TAFII transcription factor, beta subunit of G proteins.
Interactions
The way of working of the protein is based on a lot of interactions. For instance the SmRNA with and . Indeed the blade 14 is linked to the 3’side of the SmRNA and it makes a lot of interactions with . On the other side, which is the 5’ side of the SmRNA, we find the blade 8 that contains Trip 422 and EWD2. Moreover it contains which directly stacks against U5, which stacks itself against U6 . , and Asm 13 also stack against U6. Asm recognizes a base of U6. On the same model, the terminal nucleobase of U7 stacks against and WD40 domain of DDB2 recognizes dsDNA. Trp286 is located in a hydrophobic core of blade of , contacting Tyr15 which stacks against the flipped nucleotide of U6.
SmRNA is recognized through 2 grooves formed on either side of Tyr15 in and Tyr15 stacks against a flipped nucleotide of U4 . Moreover, 5’side is linked to blades 7 and 8, that helds nucleotides U3 and A2. Indeed A2 and U3 are attached by hydrogen bonds because of the guanidinium group of Arg333 which is between A2 and U3. They stack against each other as well as A1.
To further characterize the role of residues involved in SmRNA binding we mutated several conserved residues in Gemin5-WD, wich allowed us to get these results. It shows a real connection between all thoses parts.
Disease
The SMN plays an important role and its deficiency can tend to a degenerative disease linked to the motor neurons. It is called the SMA (spinal muscular atrophy) and made a disfunction in the expression of SMN1 that codes for the synthesis of the protein of the SMN complex. It is the second common recessive disease after cystic fibrosis. The death of neurons causes a paralysis of some members and weaknesses in every muscle of the body. The disease can occur four different ways:
- Type I: it is the most extreme form of the disease that is diagnosed at birth. The patient has no hope of living, life expectancy: 2 years. The ill child is not able to sit or to walk.
- Type II: it is possible to detect it since the age of 6 months. It is characterized by an incapacity to independently walk but a capacity to sit.
- Type III: it is the last juvenile form. There are less consequences than in the two other forms, ill people can do both activities without any help.
- Type IV: it only affects adults and the conséquences are a weakness of the different muscles due to hypotonia. [2] [3]
References
- ↑ Tang X, Bharath SR, Piao S, Tan VQ, Bowler MW, Song H. Structural basis for specific recognition of pre-snRNA by Gemin5. Cell Res. 2016 Dec;26(12):1353-1356. doi: 10.1038/cr.2016.133. Epub 2016 Nov 11. PMID:27834343 doi:http://dx.doi.org/10.1038/cr.2016.133
- ↑ Rossoll W, Bassell GJ. Spinal muscular atrophy and a model for survival of motor neuron protein function in axonal ribonucleoprotein complexes. Results Probl Cell Differ. 2009;48:289-326. doi: 10.1007/400_2009_4. PMID:19343312 doi:http://dx.doi.org/10.1007/400_2009_4
- ↑ Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al.. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995 Jan 13;80(1):155-65. PMID:7813012
