Ras Protein and Pancreas Cancer: Difference between revisions

Ras proteins are the founding members of a large superfamily of monomeric small GTPases. These proteins are best known for their ability to serve as molecular switches regulating diverse cellular processes that include cell cycle progression, cell survival, actin cytoskeletal organization, cell polarity and movement, and vesicular and nuclear transport <ref name=Gervaise>doi:10.1002/bip.22840</ref>. Both unicellular and multicellular organisms express Ras proteins. The human Ras superfamily is divided into five major branches: Ras proteins, Rho, Ran, Rab, and “unclassified” sequences <ref name='Gervaise'>doi:10.1002/bip.22840</ref>. Even though, these are separated branches, they share a lot of similarities not only in their structure but also in their functions.  

1CTQ has three functions, the first one is GDP and GTP binding which consist in the interaction in a non-covalent way with guanosine diphosphate and guanosine triphosphate. The second one involves the catalysis of GTP and water having as a result GDP and phosphate. The third one and not less important, is the interaction to the end part of a polypeptide chain where the terminal group is carboxyl; and this carboxyl isn’t performing its function of attaching to an amino acid residue. It is an important molecule because acts in signal transduction so that means that it activates a receptor and sends information from inner part of the cell to the outer part. It coordinates the activities different cells however if this one fails in sending wrong information it can be harmful and diseases can be present <ref name='Mueller'>doi:10.1002/bip.22840 </ref>. To get a better understanding of G proteins, we must know their function.  G Proteins act as switches that regulate information in the cell, it can activate or deactivate. It acts a signaling protein which sends information to the cell receptors to a variety of effectors. These proteins are all found in eukaryotic cells, and they control metabolic, humoral, neural, and developmental functions. More than a hundred different kinds of receptors and many different effectors have been described (MI Simon, 1991).  

The absence or mutations of these proteins cause major diseases, cancers in lungs, bladder, pancreas, and heart are the most common but not the only ones. These proteins are very important for everything because they control a lot of functions in cells. the absence or mutations of these signaling proteins can cause terrible damage in our body. I want to talk about the gene KRas which produces the KRas protein, this protein participates in cellular signaling, it controls the growth and death of cells. The normal form of this protein is natural KRas but when it gets mutated we can find different types of cancer such as lung, colorectal and pancreas. Having these changes (mutations) we might have a possible stimulation in the cells’ growth causing this the spreading of the cells in the body. Is key to verify if the tumor has the shape of a mutated or natural KRas gene so that the treatment of the cancer can be planified.   

Proteins are structured with alpha helices and beta sheets, in this case Ras proteins are made up of five alpha helices and 6 beta sheets. The diphosphate-binding loop G1 (also known as P-loop), with the consensus sequence, connects the β1 strand to the α1 helix and contacts the α- and βphosphates of the guanine nucleotide. The connection between the α1 helix and the β2 strand corresponds to G2 and contains a conserved <scene name='81/814069/Thrmg/1'>threonine residue</scene> (Thr35) involved in Mg2+coordination. The G3 domain, at the NH2 terminus of the <scene name='81/814069/Helixbase/1'>α2 helix</scene>, links the sites for binding Mg2+ and the γ-phosphate of GTP. The G4 domain that links the β5 strand and the α4 helix recognizes the guanine ring. The G5 loop, located between β6 and helix α5, reinforces the guanine base recognition site <ref name='Gervaise'>doi:10.1002/bip.22840</ref>. Ras proteins act as connectors which connect the interior of the cell with the cell surface <ref name='Gervaise'>doi:10.1002/bip.22840</ref>. The binding to GTP and GDP determines whether they are activated or not, they undergo a conserved mechanism: Ras functions require the participation of distinct regulatory proteins to control the GDP/GTP cycling rate <ref name='Gervaise'>doi:10.1002/bip.22840</ref>. Indeed, the extent and duration of Ras activation in cells depends on the interplay between a variety of negative and positive regulators of the Ras cycle <ref name='Gervaise'>doi:10.1002/bip.22840</ref>.  

This is a G-protein which works as a signaling protein in humans. From the p21 Ras family, it has an A chain. It is attached by a protein-ligand binding to a magnesium ion and to <scene name='81/814069/Ligand/1'>phosphoaminophosphonic acid- guanylate ester</scene> (GNP).