Information

5: Protein Function - Biology

5: Protein Function - Biology



We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

5: Protein Function

5 Roles of Protein

Protein can be found in animal sources like meat and dairy products, or plant sources like beans, nuts and seeds. According to the USDA, 10 to 35 percent of your calorie intake should come from protein. Every cell in your body contains protein, so meeting your protein requirement is essential for your health.


5: Protein Function - Biology

Article Summary:

INTRODUCTION
Proteins have many different and varied biological functions and in addition to their size, shape and orientation, can be classified according to their biological roles within the cell.

Enzymes
Almost every chemical reaction between organic bio molecules in living cells are catalysed by enzymes. Enzymes are the most varied and specialised proteins, and many thousands of different types, each capable of catalysing a different type of chemical reaction, have been discovered in different organisms.

Nutrient and Storage Proteins
Many plants store nutrient proteins in their seeds. Such proteins are vital for the growth and survival of the germinating seedlings. Particularly well-studied examples are the seed proteins found in corn, wheat and rice. Other examples of nutrient proteins are ovalbumin, the major component protein of egg white and casein, found in milk.
Ferritin, found in some bacteria, and also in plant and animal tissues, stores iron.

Contractile Proteins
Some proteins provide cells and organisms with the ability to contract, to change conformation, or to move about, and are known as contractile or motile proteins.
Actin and myosin function in the contractile system of skeletal muscle, and are also found in many non-muscle cells. Microtubules are formed from the protein tubulin, and act in conjunction with the protein dyenin in the flagella and cilia of bacteria, which propel the organisms, allowing motility.

Transport Proteins
These proteins allow substances to be carried to their destination. In blood plasma, transport proteins bind and transport specific molecules or ions from one organ to another. Haemoglobin in erythrocytes binds oxygen as blood passes through the lungs, transporting it to the peripheral tissues, and releases it to contribute in the energy-yielding oxidation of nutrients. Blood plasma contains lipoproteins, which carry lipids from the liver to other organs. Other types of transport proteins are present in the plasma membranes and intracellular membranes of all organisms these are adapted to bund glucose, amino acids and other substances, and transport them across the membrane to the point at which they are utilised.

Structural Proteins
In order to give biological structures strength or protection, many proteins serve as supporting filaments, cables or sheets. The chief constituent of tendons and cartilage is collagen, which is a fibrous protein, having a very high tensile strength. One example of this is leather, which comprises of almost pure collagen. Ligaments contain elastin, which is a structural protein which can be stretched in two dimensions. Hair, fingernails, feathers and horn all contain great amounts of keratin, which is a tough, insoluble protein. The main component of silk fibres and spider webs is fibroin and the wing hinges of some insects contain resilin. Resilin has ideal elastic properties.

Regulatory Proteins
Cellular or physiological activity is also regulated by some proteins. Amongst those proteins are many hormones. Insulin, which regulates sugar metabolism and the growth hormone secreted by the pituitary gland are two examples. The cellular response to many hormonal signals is often mediated by a class of GTP-binding proteins, known as G proteins. GTP is closely associated to ATP, where guanine replaces the adenine section of the molecule. Other regulatory proteins attach to DNA and control the biosynthesis of enzymes and RNA molecules concerned in cell division, in both prokaryotes and eukaryotes.

Defence Proteins
Many proteins defend organisms against invasion by another species or protect them from injury. The immunoglobins or antibodies, which are specialised proteins produced by the lymphocytes of vertebrates, can recognise, precipitate or neutralise invading microorganisms, and also foreign proteins from another species. Fibrinogen and thrombin are blood clotting proteins which stop the loss of blood when damage occurs to the vascular system. Some snake venom, bacterial toxins and toxic plant proteins, such as ricin, also appear to have defensive functions. Some of these, including fibrinogen, thrombin and some types of venom, are also enzymes.

Other Proteins
There are numerous other proteins whose functions are exotic in nature and therefore, are not easily classified. Monellin, a protein from an African plant, has an intensely sweet taste and has been studied for human use as a food sweetener. Some Antarctic fish possess antifreeze proteins within their blood plasma, which prevents their blood from freezing.

About Author / Additional Info:

Important Disclaimer: All articles on this website are for general information only and is not a professional or experts advice. We do not own any responsibility for correctness or authenticity of the information presented in this article, or any loss or injury resulting from it. We do not endorse these articles, we are neither affiliated with the authors of these articles nor responsible for their content. Please see our disclaimer section for complete terms.


Proteins act as receptors on cell membranes

Proteins are essential components of all the cell membranes and membranes of the organelles. One of the functions of these membrane proteins is that they act as receptors. Hormones, neurotransmitters, and other signalling molecules bind to these receptors and convey signals to cells. In this way, proteins play a role in cell signalling that is essential for the coordinated function of all the cells present in our body. Take the following example to understand the role of proteins as receptors.

  • Insulin is a hormone that controls the glucose levels in our blood. It performs its function by binding to its receptor that is a protein. Insulin binds to its receptor that sends signals for the opening of glucose channels so that glucose can be taken up from the blood into the liver and muscle cells. If the insulin receptors are not present, the blood glucose levels cannot be regulated.

This and various other examples in our body prove why proteins are necessary for cell signalling and coordination of cellular functions.


Nonstructural protein 5 – 3C-like proteinase

The nonstructural protein 5 (nsp5, also known as 3CLpro), is the main protease of the coronavirus genome, exhibiting as main known role the cleavage of the polyproteins translated from the viral RNA viral. Dimerization of SARS-CoV-1 3CLpro is essential to stabilize the catalytic site. The dimer interface is highly conserved within SARS-CoV-1 and -CoV-2, however, substitutions may affect dimer interaction and phosphorylation pattern of 3CLpro in SARS-CoV-2. Given that the substrate binding site of SARS-CoV-2 3CLpro is very similar to PEDV 3CLpro, it is possible that SARS-CoV-2 3CLpro is also active towards NF-kB essential modulator, thus suppressing host immune response.

The nonstructural protein 5 (nsp5, also known as 3CL pro ), is the main protease of the coronavirus genome, exhibiting a main role in the cleavage of the polyproteins translated from the viral RNA (Perlman and Netland 2009 Ziebuhr, Snijder, and Gorbalenya 2000 Anand et al. 2003). This protein is highly conserved relative to SARS-CoV-1 (96% identity) and among RNA+ viruses (Nidovirales) in general, making it an attractive target for pan-antiviral drugs (Zhang, Lin, Kusov, et al. 2020 Nukoolkarn et al. 2008 Dayer, Taleb-Gassabi, and Dayer 2017). In addition, it has been shown that loss of nsp3 and nsp10 substantially reduces 3CL pro activity (Donaldson et al. 2007, Stokes et al. 2010) and therefore therapeutics that target these proteins could indirectly inhibit 3CL pro .

Structural analysis and comparison with SARS-CoV-1 nsp5 – Studies with SARS-CoV-1 show that dimerization is essential to stabilize the productive conformation of 3CL pro catalytic site. The recently solved structure of 3CLpro of SARS-CoV-2 (PDB id: 6y2e) confirms the dimer as its biological state. The dimer interface is highly conserved within SARS-CoV-1 and -CoV-2, as well as other residues that indirectly affect dimerization, such as Ser 144 , Ser 147 and Asn 28 (Barrila, Bacha, and Freire 2006). However, a relevant substitution Thr 285 Ala is found on the interface. Based on previous studies with SARS-CoV-1 3CL pro , this replacement is thought to favor the hydrophobic pack within monomers, and it was recently associated with a slightly higher catalytic efficiency of SARS-CoV-2 compared to SARS-CoV-2 (Zhang, Lin, Sun, et al. 2020). The analysis of the evolutionary tree from the aligned sequences of coronavirus from all available species reveals that alanine at site 285 defines the SARS-CoV-2 clade and three bat coronaviruses from mainland China (manuscript in review). In contrast, the many of the beta coronaviruses that infect mammals have a cysteine at this location. Given the proximity with the cysteine in the opposite monomer, it is possible that a disulfide bridge is formed in these proteases, which may result in a more tightly bound dimer and increased catalytic efficiency. Further exploration of this site is warranted.

There are 7 non-conservative amino acid substitutions between SARS-CoV-1 and SARS-CoV-2, besides Thr 285 Ala. Most of those are located in regions that are not clearly associated with protease function, except by Ala 46 Ser, positioned at the catalytic cleft entrance, which may affect substrate affinity/selectivity. Moreover, the phosphorylation of serines in 3CL pro of rotaviruses was shown to be essential for protease activity. The substitutions Ala 46 Ser, Ser 65 Asn, Ser 94 Ala, Ala 267 Ser and Thr 285 Ala may also affect the phosphorylation pattern of 3CL pro in SARS-CoV-2.


MAPs bind to the tubulin subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell types, and they have been found to carry out a wide range of functions. These include both stabilizing and destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell. [1]

Within the cell, MAPs bind directly to the tubulin dimers of microtubules. This binding can occur with either polymerized or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure, further encouraging polymerization. Usually, it is the C-terminal domain of the MAP that interacts with tubulin, while the N-terminal domain can bind with cellular vesicles, intermediate filaments or other microtubules. MAP-microtubule binding is regulated through MAP phosphorylation. This is accomplished through the function of the microtubule-affinity-regulating-kinase (MARK) protein. Phosphorylation of the MAP by the MARK causes the MAP to detach from any bound microtubules. [2] This detachment is usually associated with a destabilization of the microtubule causing it to fall apart. In this way the stabilization of microtubules by MAPs is regulated within the cell through phosphorylation.

The numerous identified MAPs have been largely divided into two categories: Type I including MAP1 proteins and type II including MAP2, MAP4 and tau proteins.

Type I: MAP1 Edit

MAP1a (MAP1A) and MAP1b (MAP1B) are the two major members of the MAP1 family. They bind to microtubules through charge interactions, a different mechanism to many other MAPs. [3] While the C termini of these MAPs bind the microtubules, the N termini bind other parts of the cytoskeleton or the plasma membrane to control spacing of the microtubule within the cell. Members of the MAP1 family are found in the axons and dendrites of nerve cells. [4]

Type II: MAP2, MAP4, and tau Edit

Type II MAPs are found exclusively in nerve cells in mammals. These are the most well studied MAPs—MAP2 and tau (MAPT)—which participate in determining the structure of different parts of nerve cells, with MAP2 being found mostly in dendrites and tau in the axon. These proteins have a conserved C-terminal microtubule-binding domain and variable N-terminal domains projecting outwards, probably interacting with other proteins. MAP2 and tau stabilize microtubules, and thus shift the reaction kinetics in favor of addition of new subunits, accelerating microtubule growth. Both MAP2 and tau have been shown to stabilize microtubules by binding to the outer surface of the microtubule protofilaments. [5] [6] A single study has suggested that MAP2 and tau bind on the inner microtubule surface on the same site in tubulin monomers as the drug Taxol, which is used in treating cancer, [7] but this study has not been confirmed. MAP2 binds in a cooperative manner, with many MAP2 proteins binding a single microtubule to promote stabilization. Tau has the additional function of facilitating bundling of microtubules within the nerve cell. [8]

The function of tau has been linked to the neurological condition Alzheimer's disease. In the nervous tissue of Alzheimer's patients, tau forms abnormal aggregates. This aggregated tau is often severely modified, most commonly through hyperphosphorylation. As described above, phosphorylation of MAPs causes them to detach from microtubules. Thus, the hyperphosphorylation of tau leads to massive detachment, which in turn greatly reduces the stability of microtubules in nerve cells. [9] This increase in microtubule instability may be one of the main causes of the symptoms of Alzheimer's disease.

In contrast to the MAPs described above, MAP4 (MAP4) is not confined to just nerve cells, but rather can be found in nearly all types of cells. Like MAP2 and tau, MAP4 is responsible for stabilization of microtubules. [10] MAP4 has also been linked to the process of cell division. [11]

Other MAPs, and naming issues Edit

Besides the classic MAP groups, novel MAPs have been identified that bind the length of the microtubules. These include STOP (also known as MAP6), and ensconsin (also known as MAP7).

In addition, plus end tracking proteins, which bind to the very tip of growing microtubules, have also been identified. These include EB1, EB2, EB3, p150Glued, Dynamitin, Lis1, CLIP170, CLIP115, CLASP1, and CLASP2.

Another MAP whose function has been investigated during cell division is known as XMAP215 (the "X" stands for Xenopus). XMAP215 has generally been linked to microtubule stabilization. During mitosis the dynamic instability of microtubules has been observed to rise approximately tenfold. This is partly due to phosphorylation of XMAP215, which makes catastrophes (rapid depolymerization of microtubules) more likely. [12] In this way the phosphorylation of MAPs plays a role in mitosis.

There are many other proteins which affect microtubule behavior, such as catastrophin, which destabilizes microtubules, katanin, which severs them, and a number of motor proteins that transport vesicles along them. Certain motor proteins were originally designated as MAPs before it was found that they utilized ATP hydrolysis to transport cargo. In general, all these proteins are not considered "MAPs" because they do not bind directly to tubulin monomers, a defining characteristic of MAPs. [13] MAPs bind directly to microtubules to stabilize or destabilize them and link them to various cellular components including other microtubules.


Protein Function Follows Form: Two-Lesson Activity

Created by Moriah Beck, Masih Shokrani, Karen Koster, William Soto, David McDonald, and David Swanson for the National Academies Northstar Institute for Undergraduate Teaching in Biology, this activity spans 2-3 classes and uses lecture, clicker questions, jigsaws, and group discussions to teach the relationship between protein structure and function. This multi-class lesson "aims to elucidate the relationship between structure and function of proteins. Proteins are introduced based on their amino acids sequence (primary structure), shape of backbone (secondary structure), folding and three dimensional shape (tertiary structure), and whether proteins contain any subunits (quaternary structure). Enzymes are proteins that catalyze various reactions. Allosteric regulation, binding of a regulatory molecule, on a site on the enzyme other than the active site, is one way enzyme activity is regulated. Allosteric regulation results in the activation or inhibition of enzyme activity. Structure and function relationship is also illustrated by depicting oxygen binding to hemoglobin molecule which correlates for hemoglobin structure and function. Change in hemoglobin primary sequence due to single point mutations is utilized to illustrate how change in the amino acid sequence will affect hemoglobin structure and function." Students gain this knowledge by

Learning Outcome(s)

Activity/assessment

Understand different levels of protein structure to emphasize flexibility/dynamic nature

Predict how changes in binding interactions affect structure and function

Mini-lecture on enzyme function, regulation, and allostery

Understand that binding of allosteric regulators can be both positive and negative

Formative assessment, clicker questions on allosteric regulation figure

Continue to probe understanding of allosteric regulation if need be

Read and understand scientific literature

Jigsaw reading assignment and guiding questions presented

Collaborate with other students interpret and predict data

Discuss group answers to reading assignment questions

Learning Outcome

Activity/Assessment

Hypothesis generation from geese flying over climber on Mt.Everest slide

Individual followed by group discussion of potential hypotheses explaining figures

Understand Hb functional properties and adaptive consequences

Mini-lecture: Hb function and regulation + Group discussion questions

Should be able to classify amino acids based on structural properties

Amino acid classification exercise

Predict how amino acid mutations will affect structure and function of Hb

Group activity: Hb structure/ function/mutations

Synthesis and prediction of how Hb structure and function will respond to hypoxia


Possible neuroprotective roles of PrP C

PrP C may have a neuroprotective role in a mouse model of cerebral ischemia, as PrP C -deficient mice show larger lesions in acute cerebral ischemia. Furthermore, overexpression of PrP C can reduce the lesion size compared to wild-type mice [121,122,123,124]. Attenuation of NMDA signaling by PrP C has been proposed to be the basis of a neuroprotective role of PrP C against NMDA-mediated toxicity in ischemia [125]. Additionally, it was found that cleavage of PrP C into its N- and C-terminal fragments is enhanced under ischemic conditions and these cleavage products can themselves be neuroprotective [124]. In particular, the N-terminal cleavage fragment (N1) might be neuroprotective against staurosporine-induced Caspase-3 activation in a model of pressure-induced ischemia in the rat retina [126]. These results are supported by several in vitro studies, where expression of PrP C was protective against staurosporine or anisomycin-induced apoptosis [127, 128]. Conversely, loss of PrP C was beneficial against glutamate-induced excitotoxicity in vitro, an effect supposedly mediated by increased uptake of glutamate in PrP C -ablated astrocytes [129].

The protective function of the N1 fragment is also very intriguing in the context of the Aβ oligomer-related synaptotoxicity. This intrinsically disordered N-terminal portion of PrP C is involved in binding to β-sheet-rich peptides like Aβ oligomers [99, 101] and mediates the detrimental effects of Aβ oligomers on synaptic function as mentioned before. However, in its soluble form as secreted upon PrP C cleavage, N1 acted in a decoy receptor-like mode: it prevented Aβ peptide fibrillization and reduced the neurotoxicity of amyloid-β oligomers in vitro and in vivo [130]. Additionally, the rate of PrP C alpha-cleavage is increased in brain tissue from patients suffering from AD and it was proposed that alpha-cleavage represents an endogenous protective mechanism against amyloid-β toxicity in humans [131].

However, PrP C -deficient mice do not exhibit altered amyloid-β toxicity [102,103,104,105] and there was no protective effect of PrP C in mouse models of other neurodegenerative diseases, including Parkinson's and Huntington's disease, as well as a mouse model of tauopathy [124, 132].

Based on in vitro studies, by virtue of its ability to bind copper, PrP C has been proposed to participate in resistance to oxidative stress by preventing reactive oxygen species (ROS) generation via free copper-mediated redox reactions. Also, PrP C was at some point thought to regulate the function of superoxide dismutase (SOD) [133]. It was even proposed that PrP C could act as a SOD by itself [27, 134]. However, a function of PrP C in copper metabolism is still controversial and the influence of PrP C on either SOD level or the intrinsic dismutase activity of PrP C was shown by us and others to be artifactual [135, 136]. There might be, however, alternative ways in which PrP C protects against ROS toxicity. For instance, PrP C -dependent expression of antioxidant enzymes was suggested as an explanation for resistance to oxidative stress mediated by PrP C [137, 138] as well as a conjectured PrP C function in iron metabolism and control of redox-iron balance in cell lines [139, 140].


Amino acids have different R groups. Some of these R groups will be hydrophilic, making the amino acid polar, while others will be hydrophobic, making the amino acid non-polar. The distribution of the polar and non-polar amino acids in a protein influences the function and location of the protein within the body. Non-polar amino acids are found in the centre of water soluble proteins while the polar amino acids are found at the surface.

Examples of how the distribution of non-polar and polar amino acids affect protein function and location:

Controlling the position of proteins in membranes: The non-polar amino acids cause proteins to be embedded in membranes while polar amino acids cause portions of the proteins to protrude from the membrane.

Creating hydrophilic channels through membranes: Polar amino acids are found inside membrane proteins and create a channel through which hydrophilic molecules can pass through.

Specificity of active site in enzymes: If the amino acids in the active site of an enzyme are non-polar then it makes this active site specific to a non-polar substance. On the other hand, if the active site is made up of polar amino acids then the active site is specific to a polar substance.


Watch the video: Βιολογία Κατεύθυνσης. Οπερόνιο της λακτόζης (August 2022).