Sandbox Reserved 350: Difference between revisions

[http://en.wikipedia.org/wiki/Coagulation_cascade Coagulation] is a complex cascade of a biological reaction that takes place after an injury causing bleeding, to prevent bleeding; A step of hemostatsis, which faccilitates the formation of fibrin.  There approiaxmetly 30 known factors which play a role in this massive cascade response.  A possible explannation for the sheer complexity associated with what is knwon about this cascade is that tight regulation for the formation of blood clots are crutial.

The role of Human Coagulation Factor V is to act as a cofactor along with Factor X and Prothrombin (Factor II, inactive) to form a [http://en.wikipedia.org/wiki/Prothrombinase Prothrombinase] complex activating Prothrobin to Thrombin (FIIa).  Thrombin is then able to activate Firinogen (Factor I) into Fibrin (FIa), which connects platelets bound at the site of injury; formation of a clot.

It is vital for controled blood clot formation based on known human diseases/conditions of irregular clotting which are quiet devastating.  Two clear aspects of blood clotting involves either under clotting or excessive clotting.  The inability to form a clot leads to excessive bleeding from a minor abration known as [http://en.wikipedia.org/wiki/Haemophilia hemophila]. <ref name="Hemo">PMID: 21453683 </ref> [http://en.wikipedia.org/wiki/Thrombosis Thrombosis] is the second case, where excessive clotting or clotting when no wound is present results in free floating embolisms or thombuses. <ref name="Throm">PMID: 21455860 </ref> Floating free in the blood allows the thrombus to lodge itself within the circulatory system, interferring with orgran downstream of the circulating blood.  Unusual blood circulation/clotting by a thrombus are causes of heart attacks, strokes and necrosis of tissue. <ref name="Throm2">PMID: 21359071 </ref>

'''The FVa-C2''', which is classified as a ''' <font color='red'> distorted jelly-roll </font> ''' <scene name='Sandbox_Reserved_350/Expriment3/1'> β-barrel motif </scene>, is compossed of <scene name='Sandbox_Reserved_350/Expriment5/1'> eight major antiparallel strands  </scene> arranged into two ''' <font color='lawngreen'> β-sheets of five </font> and <font color='maroon'> three strands </font> ''' packed against one another.

Salt bridges located within the "upper" segment ''' <font color='goldenrod'> (Asp61-Arg134) </font>.  The C2-Domain of Human coagulation factor is homologous to a larger family of adhesion proteins; [http://proteopedia.org/wiki/index.php/Category:Discoidin_family Discoidin],but not related to synaptotagmin-like C2 domains.<ref name="Pubmed"/>

Functionality of Human Coagulation Factor V (FV), as most proteins is strongly correlated to the conformation of the overall strcture.  As noted above in the structural section, two structural forms of Human Coagulation Factor V C2 Domain were crystallized.  These two structures were disctinct from each other based on a conformational change present, alternating between what was described as a Open and Closed form.  This change from close to open by exposing this groove results due to the kind of environment Human Coagulation Factor V finds itself in, and ultimately the source of it's function.  This confers that FV is not an enzymatically active protein, but instead acts a cofactor part of the larger [http://en.wikipedia.org/wiki/File:Coagulation_full.svg Cougulation Cascade.]

Originally, the activation of FV to Fva was understood to require the exision of B segment between between the heavy and light chain at Arg-1018 and Arg-1545.  The peptide as a whole remains united via the disulfide linkage connecting the N and C Terminus and interactions with calcium ions. <ref name="Old"/>  In 1999, the [[#Finer Crystallography Details| crystalization]] of FV in both Fv and Fva was identified prodividing further insight into the quaternary structure of FV and the underlining mechanism by which the protein functions. <ref name="Pubmed"/>  This mechanism proposed has three novel points, which were over-looked based on assumed knowledge from previous studies modeling the mechanism for FV after the well characterized mechanism of vitamin K-dependent [http://en.wikipedia.org/wiki/Coagulation Coagulation Factors]; [http://en.wikipedia.org/wiki/Factor_VII VII] [http://proteopedia.org/wiki/index.php/1dan (1dan)]