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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immunoglobulin isotypes

The immunoglobulin superfamily comprises an evolutionarily ancient, widely expressed, constitutive or long-term up-regulated family of glycoproteins involved in cellular adhesion, signaling, and the adaptive immune response.

Immunoglobulins (left - click to enlarge) comprise two heavy (H) and two light-chain (L) protein subunits, each of which folds into domains (4 on heavy, 2 on light). These adhesion sites or domains contain one or more folds of 60 to 100 amino acids.

Depending upon the character of the heavy chain, immunoglobulins are divided into five classes – IgG, IgD, IgE, IgA, IgM – that are expressed in different tissues (detail). The classes are further subdivided into isotypes, which have different properties in terms of complement fixation and binding affinity to immunoglobulin (Ig) receptors.

Immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a given class will have very similar heavy chain constant regions. These differences can be detected by sequence studies or more commonly by serological means (i.e. by the use of antibodies directed to these differences).
1. IgG - γ - Gamma heavy chains
2. IgM - μ - Mu heavy chains
3. IgA - α - Alpha heavy chains
4. IgD - δ - Delta heavy chains
5. IgE - ε - Epsilon heavy chains

As adhesion-signaling molecules, immunoglobulins act as B-cell receptors (BCR) that recognize (ligate) specific antigens. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two Ig heavy chains, two Ig light chains and two heterodimers of Ig-α and Ig-β. Antigens bind with greatest affinity to their cognate Ig-antibody, and hence to activated the BCR of greatest affinity.

Antigen-activated B cells proliferate and differentiate into memory B cells or plasma cells. B cell development is a tightly controlled process in which over 75% of the developing cells become apoptotic because of inappropriate immunoglobulin gene rearrangements or recognition of self antigens by Igs. Copious amounts of monoclonal antibodies are synthesized by antigen-stimulated B cell-derived plasma cells, while memory B cells remain primed for rapid activation by a repeat encounter with the initial, diffentiation activating antigen.

The enormous diversity of immunoglobulin molecules is attributable to VDJ recombination, while secondary antibody diversification is engineered by AID-induced/UNG2 assisted somatic hypermutation (SHM) or class-switch recombination (CSR), and AID-induced gene-conversion (GC). Affinity maturation is achieved are somatic hypermutation and clonal selection, which together ensure that repeated exposures to the same antigen will provoke greater antibody ligating affinity in the antibody secreted by successive generations of plasma cells.

tags [Proteins] [immunoglobulin] [isotypes] [diversity]

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PDZ domains

PDZ domains are protein interaction domains found in diverse signaling proteins in bacteria, yeasts, plants, insects and vertebrates.

They comprise ~80-90 residues folded into 6 β-strands and 2 α-helices (image), can occur in one or multiple copies, and are nearly always found in cytoplasmic proteins. The interaction between a PDZ domain and its target is usually constitutive, and the domains bind either the carboxyl-terminal sequences of proteins or internal peptide sequences. PDZ domains bind to the C-terminal 4-5 residues of their target proteins, which are frequently transmembrane receptors such as GPCRs, or ion channels. (image, image, in synapse, diagram)

The consensus binding sequence contains a hydrophobic residue, which is commonly valine or isoleucine, at the very C-terminus. Residues at the -2 and -3 positions determine specificity. PDZ domains can also heterodimerize with the PDZ domains of different proteins, potentially regulating intracellular signaling. Several PDZ domains including those of syntenin, CASK, FAP, and Tiam1 can bind to the phosphoinositide PIP2. Such PIP2-PDZ domain binding is believed to control the association of PDZ domain-containing proteins with the plasma membrane.

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