Proteins and Proteomics

Proteins are complex, macromolecules comprised of amino acids linked by peptide bonds into long chains. The sequence (primary structure) and properties of constituent amino acids generate the 3D conformational structure (tertiary and quaternary structure) that is vital to the biological function of proteins. (click to enlarge image)


Proteins are essential to the structure and biological viability of all living cells and viruses. The cellular proteome is the total cellular protein under a particular set of conditions, while the complete proteome is the sum of all potential proteomes of a cell. Proteomics has become the subject of much research in cell and molecular biology.

Proteins play a number of vital roles as:
a. Enzymes or subunits of enzymes – catalyzing cellular reactions.
b. Structural or mechanical roles – structural components of tissues, components of the cytoskeleton, centrioles, cilia and flagella, microtubules, molecular motors.
c. Intracellular and intercellular signaling functions – ion channels, receptors, membrane pumps.
d. Regulatory proteins or adaptor proteins in genetic transcription, RNA processing, spliceosomes.
e. Products of immune and inflammatory responses that aid in targetting of foreign substances and organisms.
f. Storage and transport of various ligands.
g. The source of essential amino acids.

Almost all natural proteins are encoded by DNA, which is transcribed and processed to yield mRNA, which then serves as a template for translation by ribosomes on the rough endoplasmic reticulum.

Protein roles:
● cytoskeletal protein, enzymes, ion channels, latent gene regulatory proteins, receptor proteins, 'signaling' enzymes, signaling proteins, transcription factors
● activator,
● adaptor protein, amplifier protein, anchoring protein, bifurcation protein, coincidence detector protein, effector protein, messenger protein, modulator protein, relay protein, scaffold protein, transducer protein

Specific proteins/types : § adaptor protein : cAMP receptor binding protein § CARD domains : cofactor § collagen : core histones H2A, H2B, H3, and H4 : CRE-binding protein CREB § C-reactive protein § CRP § domains : elongation factor EF § granulysin : helicases : Helicase II : heterochromatin : histone : HP1 § immunoglobulin isotypes : inducible transcription factors : LexA repressor : mCAT2 receptor : motor proteins § NF-κB : nucleosome : PcG proteins : PCNA § (pentraxins, CRP) § PH family : Polycomb group : proteome : RecA : regulatory proteins : repressor proteins : ribosomes : RPA : serine rich (SR) splicing factors : silencers : Ski7p : small nuclear ribonucleoproteins (snRNPs) : spliceosome : SR (serine rich) splicing factors : trans-acting factors : trithorax group (trxG) : UPF1 UPF2 : upstream transcription factors :

Enzymes ♦ Enzymes : ♦ activation-induced (cytidine) deaminase ♦ adenylate cyclases ♦ AID ♦ Akt : AP endonuclease (Ape1) ♦ ATPases ♦ bonds ♦ cAMP-dependent protein kinase ♦ cyclin-dependent kinases : DNA glycosylase : DNA Ligase I : DNA polymerases : DNA polymerase I : DNA polymerase beta : DNase IV ♦ energetics : exonuclease 1 : exosome : Fen1 : Flap Endonuclease FEN-1 ♦ Fyn : general transcription factors ♦ GTPases : hOGG1 : hOGG1 oxoG repair : LigIII : MAP kinase ♦ MAPKs ♦ MEK ♦ MPF : Msh2-Msh3 ♦ mTOR : MutS, MutL, and MutH : 8-oxoguanine glycosylase : oxoG repair hOGG1 : PCNA ♦ PDK1 ♦ PTEN ♦ PDK1 ♦ phosphatases ♦ phospholipases ♦ phosphodiesterases ♦ phosphorylases ♦ PIKK ♦ PI3K ♦ PKA ♦ PKB ♦ PKCs ♦ protein kinases ♦ reaction energetics ♦ receptor tyrosine kinases : RNA polymerase: Replication factor C : reverse transcriptase : ribozymes : RNA polymerase II ♦ serine/threonine kinases : spliceosomal-mediated RNA trans-splicing SMaRT : trans-splicing ribozymes ♦ UNG2 ♦ uracil-DNA glycosylase : UvrD : XRCC1 :

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tags [Proteins] [Proteomics]

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modulator proteins

Modulator proteins regulate the activity of other proteins.

Calmodulin (Ca2+-regulated modulator protein, CaM) is a ubiquitous eukaryotic intracellular calcium receptor that regulates the biological activities of many cellular proteins and transmembrane ion transporters.

Calmodulin possess four EF-hand domains that alter conformation upon binding calcium ions. Calcium ions bind to the EF-loop region, shifting the relative positions of the EF-alpha helices. (The other group of proteins that depend on calcium ions for their function belong to the annexin family, which bind calcium and phospholipids). In the absence of calcium, the α-helices in the EF-hand motif of calmodulin are in the closed conformation, almost parallel to each other. When the intracellular calcium level rises, Ca2+ ions bind to calmodulin, causing calmodulin to open into a dumbell shape and increasing CaM's binding affinity. (Nine of CaM's 148 aa residues are methionines, and 8 of these 9 Met are directly involved in binding to all target peptides.) The open conformation Ca2+-calmodulin complex binds target proteins, initiating various signaling cascades. Over a hundred proteins are known to bind calmodulin (above left are three). Calmodulin is essential for cell-cycle progression through mitosis. []molecule of month[]

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signaling proteins

Proteins and other molecules serve one or more of several types of function in signaling networks:
● cell surface
_ ● ion channels
_ ● receptor proteins
__ ● latent gene regulatory proteins
● intracellular
_ ● 'signaling' enzymes
_ ● adaptor proteins
_ ● amplifier proteins
_ ● anchoring proteins
_ ● bifurcation proteins
_ ● coincidence detectors
_ ● effector proteins
_ ● mediator molecules
_ ● messenger proteins
_ ● modulator proteins
_ ● relay proteins
_ ● scaffold proteins
_ ● second messengers
_ ● transducer proteins

Adaptor proteins link the components of signaling pathways by acting as accessories to the chief proteins in a signal transduction pathway.

Amplifier proteins are usually either enzymes or ion channels. Amplifiers increase the received signal by producing large amounts of small intracellular second messengers or by activating large numbers of downstream intracellular signaling proteins. Multiple amplification steps in a relay chain are often referred to as a signaling cascade.

Anchor proteins provide a molecular framework that orients these enzymes towards selected substrates. A-kinase anchoring proteins (AKAPs) are signal-organizing, scaffold proteins that compartmentalize the cAMP dependent protein kinase, phosphodiesterases, and a variety of enzymes that are regulated by second-messengers.

Bifurcation proteins spread the signal from one signaling pathway to others.

Coincidence detectors are signaling enzymes that are only activated by several different signals occurring together. For example, cAMP-generating adenylyl (adenylate) cyclases are modulated by G-proteins, forskolin, Ca2+/calmodulin, and other class-specific substrates.

Non-genetic classes of regulatory proteins include those target, effector proteins that are involved in special cellular functions such as signaling as receptor proteins and pumps, adhesion, chemotaxis, cellular transport and active transport, and metabolic regulation, including enzymatic action and protein degradation. Effector molecules bring about regulation by binding other molecules, and genetic effector molecules can participate in the regulation of gene expression. Modulator molecules bind to a regulatory sites during allosteric modulation, where effectors act as activators or inhibitors. (Allosteric proteins have an active (catalytic) site and an allosteric (effector) site.) Effector proteins regulate the activity of other proteins.

Integrator proteins integrate signals from two or more signaling pathways and relay the signal onward along a single pathway.

Latent gene regulatory proteins are activated by receptors at the cell surface and migrate to the nucleus, where they stimulate gene transcription.

Mediators act as molecular go-betweens in signaling cascades. Second messengers are small, readily diffusible molecules that operate in signal transduction (calcium ions, cAMP, cGMP, ceramide, diacylglycerol, inositol-1,4,5-trisphosphate).

Messenger proteins carry the signal from one part of the cell to another. For example, messengers often carry signals from the cytosol to the nucleus.

Modulator proteins regulate the activity of other proteins. Calmodulin (Ca2+-regulated modulator protein, CaM) is a ubiquitous eukaryotic intracellular calcium receptor that regulates the biological activities of many cellular proteins and transmembrane ion transporters. The Ca2+•calmodulin complex binds target proteins, initiating various signaling cascades.

Relay proteins pass the message to the next signaling component in the chain without otherwise participating.

Scaffold proteins either hold protein kinases in a latent state close to their activating cell-surface receptors, or facilitate flow of activation from one kinase to the next kinase in a signaling cascade. The A kinase anchoring proteins (AKAPs) are prototypical anchor/scaffold proteins that organize the protein kinases and phosphatases that regulate serine/threonine phosphorylation.

Transducer proteins convert the signal from one form to another. Signaling enzymes that produce cyclic AMP, for example, both convert the received signal and amplify it (transducer and amplifier).

'Signaling' domains are found in intracellular proteins that are involved in signaling cascades:
● EF hand domains
● PDZ domains
● pleckstrin homology (PH) domain family
● SH2 domains

Cell-surface adhesion interactions and inflammatory responses employ specialized domains:
● cadherin repeats
● carbohydrate-recognition domain (CRD)
● caspase recruiting domains, CARD domains
● C-lectin domain (CRD)
● C-type-lectin-like domain (CTLD)
● death domain (DD), death effector domain (DED) binds adaptor protein FADD (Fas-Associated Death Domain)
● zinc finger DNA binding domains

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