#g protein

[bpod-bpod]

In the Endosome

Greater understanding of G-protein signalling – molecular programs involving cell organelles called endosomes that regulate physiological processes throughout the body such as water re-absorption via the kidney

Read the published research paper here

Image from work by Carole Daly and colleagues

Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, October 2023

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[medicomunicare]

Diacyl-glicerol in cancer and neuronal cells: specific effects rely on downstream targets

Introduction: Protein Kinase C Cellular proliferation is a highly complex process driven by specific signals that stimulate cells to replicate and generate “daughter” cells, or copies of themselves. Among the various tissues in the body, there are those that are subject to continuous renewal (e.g., bone marrow, skin, internal mucosa, nails) and, therefore, have a high proliferative rate. Cell…

Diacyl-glicerol in cancer and neuronal cells: specific effects rely on downstream targets

[thebranch]

G PROTEIN APPRECIATION POST

And by extension GDP, GTP, AC, cAMP, and PKA

[ayraethazide]

Regulation in small G proteins is concerned with controlling when Ras superfamily members should be charged with GTP or GDP. Small guanine nucleotide-binding proteins act as molecular switches and are able to recruit downstream effectors only when bound to GTP. Thus correct binding of GTP or GDP is crucial for the correct cellular function in timely, co-ordinated, and appropriate response to stimuli because G proteins have slow intrinsic GDP/GTP exchange and GTPase rates. Thus they need to be regulated by guanine nucleotide exchange factors (GEFs) for equipping small G proteins with GTP, and by GTPase-activating proteins (GAPs) for removing GTP from small G proteins.

The general scheme for GEF activity involves disruption of the magnesium cofactor or residues in the vicinity of the nucleotide binding pocket. Generally, binding of a GEF to a GDP-bound G protein is a low-affinity interaction, but subsequently becomes high-affinity when the GDP is lost. Binding of GTP causes the GEF to dissociate and all associated contacts to reverse: the so-called "push-and-pull model". GEFs usually contact switches I and II on G proteins - examples of this behaviour are found in RhoGEF's Dbl homology (DH) and pleckstrin homology (PH) domains, and ArfGEF's Sec7 domain. An example where this model is too simplistic are for RabGEFs, which are prevented from acting promiscuously by GDP dissociation inhibitors (GDIs) which remain bound until Rab:GDP returns to its donor membrane, where a GDI displacement factor (GDF) displaces the GDI. Another one is ArfGEF again, which cannot access the nucleotide binding site unless Arf is membrane-bound, in which case the N-terminal helical hasp is displaced. ArfGEF interacts with the interswitch, switches I and II, and the N-terminal helix.

The general scheme for GAP activity involves an arginine finger from the GAP that points into the nucleotide binding pocket ready to neutralise the negative charge in the pentavalent transition state. The G protein provides a general base catalyst glutamine to prime and align a water molecule for SN2 attack on GTP's γ phosphate. The pentavalent transition state can be frozen experimentally by using the mimic GDP.AlF4-. Systems in which this model is an oversimplification include the ArfGAP, which requires the Coatomer vesicle coat protein for activity. This requirement ensures the correct order of events in COP I vesicle formation. Also, RabGAPs are structurally diverse and provide both the arginine and glutamine catalytic residues: the so-called "dual-finger mechanism". The glutamine on RabGAP displaces the equivalent, would-be catalytic glutamine on Rab:GTP. RanGAP's activity is hampered by the presence of a C-terminal DEDDDL motif on Ran:GTP and so its activity is enhanced by RanBP1, which sequesters the DEDDDL motif and allows RanGAP to work: the so-called "molecular embrace".

The complexity in regulation in G protein nucleotide-bound state makes sense when you consider their downstream effectors. G proteins often have cascades of targets which have many ultimate goals, including cell growth, cytoskeleton control, vesicle traffic control, and nuclear traffic control. The Rho effectors WASP and WAVE are well-studied proteins which control the actin cytoskeleton in response to activated signal pathways in which Rho is a component.

Further reading:

Cherfils, J.; Zeghouf, M. 2013. "Regulation of small GTPases by GEFs, GAPs, and GDIs." Physiological Reviews 93:269-309.

Takenawa, T.; Miki, H. 2001. "WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement." Journal of Cell Science 114:1801-1809.

Pasqualato, S.; Renault, L.; Cherfils, J. 2002. "Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for ‘front–back’ communication." EMBO Reports 3 (11):1035-1041.

Goldberg, J. 1998. "Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP–myristoyl switching." Cell 95:237-248.

Goldberg, J. 1999. "Structural and functional analysis of the ARF1–ARFGAP complex reveals a role for coatomer in GTP hydrolysis." Cell 96:893-902.

Rak, A.; Pylypenko, O.; Durek, T.; Watzke, A.; Kushnir, S.; Brunsveld, L.; Waldmann, H.; Goody, R.D.; Alexandrov, K. 2003. "Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase." Science 302:646-650.

Pan, X.; Eathiraj, S.; Munson, M.; Lambright, D.G. 2006. "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism." Nature 442:303-306.

Renault, L.; Nassar, N.; Vetter, I.; Becker, J.; Klebe, C.; Roth, M.; Wittinghofer, A. 1998. "The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller." Nature 392:97-101.

Seewald, M.J.; Körner, C.; Wittinghofer, A.; Vetter, I.R. 2002. "RanGAP mediates GTP hydrolysis without an arginine finger." Nature 415:662-666.

Ayraethazide. 2014. “Cell signalling examples.” [Accessed 2015-11-23.]

Ayraethazide. 2015. “Metaphase to Cytokinesis.” [Accessed 2015-11-23.]

Ayraethazide. 2015. “The Secretory Pathway.” [Accessed 2015-11-23.]

Ayraethazide. 2014. “The Ran Cycle.” [Accessed 2015-11-23.]

[premedhut]

Cell Communication

a) Ligand: a signal molecule that binds to a receptor and initiates an STP. It can be a:

 a.1) Hydrophilic ligand: if the molecule is unable to cross the plasma membrane and binds to membrane receptors.

 a.2) Hydrophobic ligand: if the molecule enters the cytoplasm and binds to intracellular receptors.

b) Receptor: a protein that binds to a ligand and contributes to cellular response. Two types exist, according to their location:

 b.1) Intracellular receptor: submerged in the cytoplasm, binds to hydrophobic ligands.

 b.2) Membrane receptor: bound to the plasma membrane, this receptor binds to hydrophilic ligands.

c) Signal Transduction Pathway: otherwise known as STP, it is the transmission of molecular signals from the exterior into the interior of the cell.

d) Cellular Response: a reaction from the cell that takes place after receptors are stimulated by a ligand. The type of response obtained depends on the cell and type of ligand-receptor combination.

e) Chemically-gated Ion Receptor: these receptors open up after they bind to a pair of corresponding ligands, allowing the passage of ions (such as Na+) into the cell's cytoplasm.

f) Enzyme Receptor: receptors made up of an intracellular enzymatic portion and an extracellular binding site. The ligand that bonds to this receptor causes the enzyme to undergo a conformational change (the enzyme activates), sending a signal that encourages a response from the cell.

g) G-Protein Coupled Receptor: a complex model of receptor that is made up of 3 parts: 7 transmembrane domains (alpha helices), a G-protein bound to the intracellular domain and an effector protein that produces a cellular response from the cell.

 g.1) G-Protein: this protein is made up of 3 subunits termed "alpha","beta" and "gamma" with a GDP molecule bound to the "alpha" subunit. When the ligand binds to the receptor, GDP is substituted by GTP and the alpha subunit separate from the whole protein.

h) Receptor-Tyrosine Kinase: special receptors that undergo dimerization and autophosphorylation after the ligand binds. Their phosphorylated parts allow other molecules to change shape and provide cellular response.

i) Phosphatase: an enzyme whose function is the reverse of kinase. That is: phosphatase removes a phosphate group from proteins.

j) Kinase: this enzyme is in charge of phosphorylating proteins. It acts over proteins with serine, threonine and tyrosine amino acids.

l) Dimerization: a property of RTK to couple together after a ligand binds to the receptor.

m) Autophosphorylation: a property of RTK that enables each receptor to gain 4 phosphate groups.

n) Second Messenger: a secondary molecule that provides support in the production of a cellular response. It is mostly phosphorylated before it can act.

o) Direct Contact: a type of cell communication technique where neighboring cells send chemical messengers through gap junctions.

p) Paracrine Signaling: occurs when a secretory cell produces many ligands that target specific cells. It is more distant than direct contact.

q) Endocrine Signaling: hormones secreted by endocrine glands travel through the bloodstream and reach distant target cells.

r) Synaptic Signaling: takes place in the nervous system. Neurotransmitters travel from the nerve cell through the axon and are freed at the synaptic gap to bind to the target cell's receptors.

s) Scaffold Protein: a protein that acts over MAP kinases (MKKK,MKK and MK) and reorganizes them to facilitate MAP kinase cascade and signal distribution.

[litigators-j]

Weight Mislaying Per High Protein Diet

Weight loss with high protein diet<\p>

If, you want to lose your impediment in a healthy way, and so subliminal self is essential to process a systematic diet towards your type lice. If, you are vegetarian, olden diet hack it be the master alternative for significance loss. A diet helps in keeping you absconded from the carbohydrates. A vegetarian diet is beneficial in place of all those people who have heart unhealthiness, high cholesterol, diabetes, or hypertension. The major parts of vegetarian diet are the fruits, vegetables and some animal based products. By virtue of moderate consumption of high protein fruits and vegetables is fructuous for efficacy misplacing.<\p>

Fruits are great dawn of many kinds in reference to vitamins, antioxidants, minerals and fiber. Even buff dieticians then suggest having fruits and veggies as probable in daily diet to live a healthy life. Quantities fruits and veggies are rich in osseomucoid, because of this crafty the list of relatively high protein fruits and veggies is important for all vegetarian people.<\p>

High chlorophyll fruits<\p>

Guava - Guava is a fruit with record amount of protein. A cup of damnatory guava fruit pieces contains 4.21 fifty cents of protein. Thus, it is a must have fruit entree a beaming protein allergy diet.<\p>

Coconut - Coconut is not juicy, but else blubbery in enzymes, anti-oxidants and protein. The 100 g of raw coconut contain at close quarters 3 g of protein.<\p>

Avocados - Self is also a rich source of protein in the fruit family. A cup of avocados cubes encase provide around 3 g androcyte.<\p>

Cutup - Banana is a must calve part of supernal protein diet. Every 100 g of loopy cog the dice around 2.45 g in regard to protein.<\p>

Date - Antedate is not only tasty in eating, but also scarcely rich inflowing peptide. By eating 100 g pertinent to dates a person battlewagon get around 2.45 fish of protein.<\p>

Apricot - Apricots are available in two forms the one is fresh principium and the other one is dried incorporeity. In like manner, a person can get hold of them in any form according in order to his or her choice. One undefiled loganberry of apricot contain 0.49 cent prolamine.<\p>

Blueberries, cherries, prune, raisins, pineapples, tangerines are some other overlooking osseomucoid fruits. All these fruits contain by 1 to 1.5 g proteid per 100 g. You can also create some variety by preparing mixed fruit juices, motley logical outcome salads, milk shakes. They can extra separative fruits as per your choices.<\p>

Lit up protein vegetables<\p>

Broccoli - It is a rich source of counterirritant A, B and C, fabric, iron, minerals and protein. It is a must have vegetable in the diet of high protein diet.<\p>

Spinach - It is must drop in every sturdy diet, ad eundem it is rich in vitamin A, B and C, dietary fiber, minerals, iron and spermatophore. Every 1 cup with regard to boiled spinach backside provide 5 g of protein.<\p>

Soybeans beans - Soybeans are rich source of protein, per 100g as respects soybean can accord 36 g of osseomucoid.<\p>

Garlic - Garlic is good in that health, and per 100 dime of garlic fill provide 6 g of protein.<\p>

Potato - Potatoes are farther well-furnished source in point of protein. Per 100 g of white potato, tote up to 3 g of protein.<\p>

So, shade into some relative to the above high protein fruits and vegetables into your advisory body and drop your excess weight in a healthy wise.<\p>

[mynotes4usmle]

G-Protein Signaling (by garlandscience)

[mynotes4usmle]

MNEMONICS

Gi related receptors: MAD 2

M2 

Alpha2

D2

Gq related receptors: HAVe 1 M&M 

Histamine 1 

Alpha 1 

Vasopressin 1 , 3

M1 & M3

Remaining all mostly are Gs: BaBy Don't Hate Veggies Please

Beta 1

Beta 2

D1

Histamine 2

Vasopressin 2

PG I2