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overview

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.

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.

myoglobin, mod. gjh.md

Proteins play a number of vital roles as:
Enzymes or subunits of enzymes -- catalyzing cellular reactions.
Structural or mechanical roles -- structural components of tissues, components of the cytoskeleton, centrioles, cilia and flagella, microtubules, molecular motors.
Intra- and intercellular signalling functions -- ion channels, receptors, membrane pumps.
Regulatory proteins in genetic transcription, RNA processing, spliceosomes.
Products of immune response that aid in targetting of foreign substances and organisms
Storage and transport of various ligands.
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 at the rough endoplasmic reticulum.

Structure of a protein, public domain

Item links

overview / apoptosis: Bcl-2 proteins / BER glycosylases / caspases / DNA damage: eukaryotic response: NKG2D: RNR / DNA repair enzyme : hOGG1 / heat shock proteins / hedgehog & smoothened & primary cilium / histone proteins / p53

apoptosis: Bcl-2 proteins

Apoptosis - Bcl-2 proteins: "The bcl-2 proteins are a family of proteins involved in the response to apoptosis. Some of these proteins (such as bcl-2 and bcl-XL) are anti-apoptotic, while others (such as Bad or Bax) are pro-apoptotic. The sensitivity of cells to apoptotic stimuli can depend on the balance of pro- and anti-apoptotic bcl-2 proteins. When there is an excess of pro-apoptotic proteins the cells are more sensitive to apoptosis, when there is an excess of anti-apoptotic proteins the cells will tend to be less sensitive."

BER glycosylases

MOLECULAR BIOLOGY: ON DNA-REPAIR ENZYMES: Base excision repair (BER) is a specialized pathway that plays a primary role in repairing damaged DNA bases. The damaged base is first removed by specific BER glycosylases, followed by excision of the remaining sugar fragment, and finally, installation of an undamaged nucleotide by a DNA polymerase. Of note, inherited defects in BER have recently been linked to colorectal cancer.

caspases

Apoptosis: "Caspases (cysteinyl aspartate-specific proteases) are enzymes that cleave specific proteins at aspartate residues. They contain cysteine residues in their active sites. Many caspase isoforms promote apoptosis. They can be activated by two main pathways: the death receptor pathway and the mitochondrial pathway.

At least 14 caspase isoforms have now been identified. These isoforms are broadly categorised into initiators, effectors and inflammatory caspases. Initiator caspases such as caspase-8 and 9 cleave and activate effector caspases such as caspase-3. Effector caspases cleave specific proteins that ultimately leads to cell death by apoptosis. Caspase activity leads to a proteolytic cascade in which one caspase can activate other caspases. This amplifies the apoptotic signalling pathway.

Cleavage of proteins by caspases can either activate them (e.g. other caspases and ICAD), or they can deactivate them (e.g. PKB/Akt, Raf-1 and PARP-1). Generally, proteins that promote apoptosis are activated, and proteins that promote survival are inactivated." MORE

DNA repair enzyme : hOGG1

MOLECULAR BIOLOGY: ON DNA-REPAIR ENZYMES: "hOGG1 makes extensive contacts with the orphaned cytosine base, which ensures that oxoG is removed only when in the appropriate base-pairing context. Although extensive biophysical and structural studies intimate that there are general features of damaged bases that signal their presence to repair enzymes, the steps involved in finding damaged bases in a sea of normal ones are still unclear. Most mechanisms invoke the enzyme sliding or hopping along the DNA duplex until a damaged site is detected. A particularly intriguing question is whether normal bases are also extruded from the helix during the search process."

DNA damage: eukaryotic response: NKG2D: RNR

Natural killer cells: DNA damage link to innate immunity - Cell Signaling Update - Signaling Gateway: "NKG2D (natural-killer group 2, member D) is an activating receptor that is expressed at the surface of natural killer (NK) cells and CD8+ T cells. NKG2D recognizes ligands that are upregulated by diseased cells, leading to the lysis of these cells"

MRC Radiation and Genome Stability Unit: "Radiation-induced damage in DNA has been shown to migrate and localise at guanine "

dNTP : "In eukaryotes, DNA damage elicits a multifaceted response that includes cell cycle arrest, transcriptional activation of DNA repair genes, and, in multicellular organisms, apoptosis. We demonstrate that in Saccharomyces cerevisiae, DNA damage leads to a 6- to 8-fold increase in dNTP levels. This increase is conferred by an unusual, relaxed dATP feedback inhibition of ribonucleotide reductase (RNR). Complete elimination of dATP feedback inhibition by mutation of the allosteric activity site in RNR results in 1.6-2 times higher dNTP pools under normal growth conditions, and the pools increase an additional 11- to 17-fold during DNA damage. The increase in dNTP pools dramatically improves survival following DNA damage, but at the same time leads to higher mutation rates. We propose that increased survival and mutation rates result from more efficient translesion DNA synthesis at elevated dNTP concentrations."

Chabes A, Georgieva B, Domkin V, Zhao X, Rothstein R, Thelander L.
Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase.
Cell. 2003 Feb 7;112(3):391-401.
Comment on: Cell. 2003 Feb 7;112(3):286-7.