Sandbox Reserved 350
From Proteopedia
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| - | :Protein: cHuman Coagulation factor V, 1czv <ref name="Pubmed"> 10586886 </ref> | + | :Protein: cHuman Coagulation factor V, 1czv <ref name="Pubmed">PMID: 10586886 </ref> |
{{STRUCTURE_1czv|PDB=1czv|SCENE=}} | {{STRUCTURE_1czv|PDB=1czv|SCENE=}} | ||
__TOC__ | __TOC__ | ||
=Structure= | =Structure= | ||
| - | The structure of Human Coagulation Factor V (FV) is sculpted from, originates from, precursors from a translated polypeptide to a A1-A2-B-A3-C1-C2 layout which results in the activated (FVa) protein. | + | The structure of Human Coagulation Factor V (FV) is sculpted from, originates from, precursors from a translated polypeptide to a A1-A2-B-A3-C1-C2 layout which results in the activated (FVa) protein.<ref name="Pubmed"/> |
<br /> | <br /> | ||
*'''Heavy A1-A2 Chain''' | *'''Heavy A1-A2 Chain''' | ||
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*'''Light A3-C1-C2 Chain''' | *'''Light A3-C1-C2 Chain''' | ||
| - | FVa consists of a conserved '''β-Barrel framework''' acting as a scaffold for three loops and a '''C2 domain''' (FVa-C2). | + | FVa consists of a conserved '''β-Barrel framework''' acting as a scaffold for three loops and a '''C2 domain''' (FVa-C2).<ref name="Pubmed"/> |
<br /> | <br /> | ||
'''The FVa-C2''', which is classified as a '''distorted jelly-roll β-barrel motif''', is compossed of e'''ight major antiparallel strands''' arranged into two '''β-sheets of five and three strands''' packed against one another. | '''The FVa-C2''', which is classified as a '''distorted jelly-roll β-barrel motif''', is compossed of e'''ight major antiparallel strands''' arranged into two '''β-sheets of five and three strands''' packed against one another. | ||
<br /> | <br /> | ||
Salt bridges located within the "upper" segment (Asp61-Arg134)'''--Fig2.--''' and the "lower" segment considered basic, due to the XXX '''basic residues''' present in number and alkalinity?. Both together.. | Salt bridges located within the "upper" segment (Asp61-Arg134)'''--Fig2.--''' and the "lower" segment considered basic, due to the XXX '''basic residues''' present in number and alkalinity?. Both together.. | ||
| - | The C2-Domain of Human coagulation factor is homologous to a larger family of adhesion proteins; Discoidin,but not related to synaptotagmin-like C2 domains. | + | The C2-Domain of Human coagulation factor is homologous to a larger family of adhesion proteins; Discoidin,but not related to synaptotagmin-like C2 domains.<ref name="Pubmed"/> |
<br /> | <br /> | ||
| - | <big><ins>'''The Three Loops'''</ins></big> | + | <big><ins>'''The Three Loops'''</ins></big><ref name="Pubmed"/> |
<br /> | <br /> | ||
*(1)-Ser21-Trp31; Apex containing Indole moieties able to form hydrogen bonds (Two consecutive Trp 26 & 27). | *(1)-Ser21-Trp31; Apex containing Indole moieties able to form hydrogen bonds (Two consecutive Trp 26 & 27). | ||
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<br /> | <br /> | ||
:The apexes of these three loops within the C2 domain, are able to create a deep groove lined by hydrophobic | :The apexes of these three loops within the C2 domain, are able to create a deep groove lined by hydrophobic | ||
| - | (Trp31, Met83) and polar residues (Gln48, Ser78), as seen and xxxx the '''"Open Form"''' of FVa-C2. This groove is seen as the primary membrane-binding site of the C2-Domain. Link to Function.. maybe? | + | (Trp31, Met83) and polar residues (Gln48, Ser78), as seen and xxxx the '''"Open Form"''' of FVa-C2. This groove is seen as the primary membrane-binding site of the C2-Domain.<ref name="Pubmed"/> Link to Function.. maybe? |
<br /> | <br /> | ||
A second dimeric crystal form of FVa-C2, packed through the free edges of S6 strands, presenting a different Leu104-Val109 | A second dimeric crystal form of FVa-C2, packed through the free edges of S6 strands, presenting a different Leu104-Val109 | ||
| - | loop, suggesting capabilities of adopting a "Closed Form". In contrast to the "Open Form" of FVa-C2; when looking at the loops 1 and 3 are tilted towards the interior of the groove. This change is considered due to a twist around '''Gly28''' cause it to be deformed (pseudo). In general there is a narrowing of the entrance to the shallow inner loop groove, particularly the critical Gln48 carboxamide; Took place due form the concerted tilting/ "twisting" of the main chain atoms, shifting up to ~7Å and a 12Å displacement of the Trp27 moiety <big>→</big> shifting closer to the other two loops. Once shifted closer, the groove seen in the '''Open Form''' is covered by a hydrophobic ridge of Trp27, Trp27 and Leu79, and now in the '''Closed Form''' with a smaller, [[=Function=|370Å hydrophobic surface compared to 520Å.]] | + | loop, suggesting capabilities of adopting a "Closed Form". In contrast to the "Open Form" of FVa-C2; when looking at the loops 1 and 3 are tilted towards the interior of the groove. This change is considered due to a twist around '''Gly28''' cause it to be deformed (pseudo). In general there is a narrowing of the entrance to the shallow inner loop groove, particularly the critical Gln48 carboxamide; Took place due form the concerted tilting/ "twisting" of the main chain atoms, shifting up to ~7Å and a 12Å displacement of the Trp27 moiety <big>→</big> shifting closer to the other two loops. Once shifted closer, the groove seen in the '''Open Form''' is covered by a hydrophobic ridge of Trp27, Trp27 and Leu79, and now in the '''Closed Form''' with a smaller, [[=Function=|370Å hydrophobic surface compared to 520Å.]]<ref name="Pubmed"/> |
<br /> | <br /> | ||
Gln48 is crutial for some kind of actions of the entire Protein. ~Different colour, then link it to the Function Section. | Gln48 is crutial for some kind of actions of the entire Protein. ~Different colour, then link it to the Function Section. | ||
<br /> | <br /> | ||
| - | The three loops are described by ''Authors of the paper'' to protrude like spikes from the bottom of the barrel in monomeric FVa-C2. It is also worth noting that spike (1) & spike (3) are separated by β-hairpin structures and spike (2) is described as a wider irregularly loop comparatively. These three loops extending from the C2 domain, are all linked to each other, and to '''three shorter loops''' by an intricate '''H-bonding network''' which extends to residues at the bottom of the β-barrel. | + | The three loops are described by ''Authors of the paper'' to protrude like spikes from the bottom of the barrel in monomeric FVa-C2.<ref name="Pubmed"/> It is also worth noting that spike (1) & spike (3) are separated by β-hairpin structures and spike (2) is described as a wider irregularly loop comparatively. These three loops extending from the C2 domain, are all linked to each other, and to '''three shorter loops''' by an intricate '''H-bonding network''' which extends to residues at the bottom of the β-barrel.<ref name="Pubmed"/> |
<br /> | <br /> | ||
The overall Barrel structure is closed at the top and bottom by '''three''' and '''two''' straight segments, giving it an '''overall spherical shape''' with a flattened upper surface. | The overall Barrel structure is closed at the top and bottom by '''three''' and '''two''' straight segments, giving it an '''overall spherical shape''' with a flattened upper surface. | ||
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<br /> | <br /> | ||
<br /> | <br /> | ||
| - | The C2 domain of FVa is essential for bidning to phosphatidyl-ʟ-serine (P<sub>ʟ</sub>S)<br /> | + | The C2 domain of FVa is essential for bidning to phosphatidyl-ʟ-serine (P<sub>ʟ</sub>S)<br /><ref name="Pubmed"/> |
===Experimental Evidence=== | ===Experimental Evidence=== | ||
=References= | =References= | ||
<references/> | <references/> | ||
Revision as of 00:25, 17 March 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
To get started:
More help: Help:Editing |
Introduction
- Protein: cHuman Coagulation factor V, 1czv [1]
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| 1czv, resolution 2.40Å () | |||||||||
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| Related: | 1czs, 1czt | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Structure
The structure of Human Coagulation Factor V (FV) is sculpted from, originates from, precursors from a translated polypeptide to a A1-A2-B-A3-C1-C2 layout which results in the activated (FVa) protein.[1]
- Heavy A1-A2 Chain
- Light A3-C1-C2 Chain
FVa consists of a conserved β-Barrel framework acting as a scaffold for three loops and a C2 domain (FVa-C2).[1]
The FVa-C2, which is classified as a distorted jelly-roll β-barrel motif, is compossed of eight major antiparallel strands arranged into two β-sheets of five and three strands packed against one another.
Salt bridges located within the "upper" segment (Asp61-Arg134)--Fig2.-- and the "lower" segment considered basic, due to the XXX basic residues present in number and alkalinity?. Both together..
The C2-Domain of Human coagulation factor is homologous to a larger family of adhesion proteins; Discoidin,but not related to synaptotagmin-like C2 domains.[1]
The Three Loops[1]
- (1)-Ser21-Trp31; Apex containing Indole moieties able to form hydrogen bonds (Two consecutive Trp 26 & 27).
- (2)-Asn39-Asn45; Apex capped with a basic residue able to form hydrogen bonds (Arg43).
- (3)-Gly75-Tyr84; Apex Hydrophobic (Leu79).
- The apexes of these three loops within the C2 domain, are able to create a deep groove lined by hydrophobic
(Trp31, Met83) and polar residues (Gln48, Ser78), as seen and xxxx the "Open Form" of FVa-C2. This groove is seen as the primary membrane-binding site of the C2-Domain.[1] Link to Function.. maybe?
A second dimeric crystal form of FVa-C2, packed through the free edges of S6 strands, presenting a different Leu104-Val109
loop, suggesting capabilities of adopting a "Closed Form". In contrast to the "Open Form" of FVa-C2; when looking at the loops 1 and 3 are tilted towards the interior of the groove. This change is considered due to a twist around Gly28 cause it to be deformed (pseudo). In general there is a narrowing of the entrance to the shallow inner loop groove, particularly the critical Gln48 carboxamide; Took place due form the concerted tilting/ "twisting" of the main chain atoms, shifting up to ~7Å and a 12Å displacement of the Trp27 moiety → shifting closer to the other two loops. Once shifted closer, the groove seen in the Open Form is covered by a hydrophobic ridge of Trp27, Trp27 and Leu79, and now in the Closed Form with a smaller, 370Å hydrophobic surface compared to 520Å.[1]
Gln48 is crutial for some kind of actions of the entire Protein. ~Different colour, then link it to the Function Section.
The three loops are described by Authors of the paper to protrude like spikes from the bottom of the barrel in monomeric FVa-C2.[1] It is also worth noting that spike (1) & spike (3) are separated by β-hairpin structures and spike (2) is described as a wider irregularly loop comparatively. These three loops extending from the C2 domain, are all linked to each other, and to three shorter loops by an intricate H-bonding network which extends to residues at the bottom of the β-barrel.[1]
The overall Barrel structure is closed at the top and bottom by three and two straight segments, giving it an overall spherical shape with a flattened upper surface.
Which once activated, enhances the ability of factor Xa to generate α-thrombin from prothrombin (5-Fold).
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Some of the bold sections in this are potential green links
Function
General intro to Function..
Functionality..
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Interactions
The C2 domain of FVa is essential for bidning to phosphatidyl-ʟ-serine (PʟS)
[1]
Experimental Evidence
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature. 1999 Nov 25;402(6760):434-9. PMID:10586886 doi:10.1038/46594
