chp 3 cell bio

• Polypeptide: linear seq of amino acids found into local helices or sheets that pack unto a complex 3-dimensional shape. Some individual polypeptides associate into multichain complexes (quaternary structure) which in some cases cam be very large consisting of tens to hundreds of subunits (surpramoL complexes)
• polypeptide functions: structural, regulation, signaling, transport, catalyzing chemical reactions via enzyme & generating force for movement (via motor proteins)
• Primary structure -> Amino acids (20 in total) : organic moL w amino and carboxyl gp

  Amino acids differ in their properties due to diff side chains : R group

  Linked by cb "peptide bonds"

  Polypeptide : polymer of amino acids

  Range in length from anew to more than +++ monomers Each polypeptides has a unique linear seq of amino acids w a C terminus & N terminus
• Secondary structure : region mainly stabilized by hb btw atoms of the polypetide backbone

  Alpha helix & Beta pleated sheet
• Tertiary structure : overall 3-D shape of polypeptide stabilized by interactions btw side chain (Rgp) rather than interactions btw backbone consituenetn

  • These interactions include hb, ionic bonds, hydrophobic interactions and VdW interactions
  • Strong cv called disulfide bridges may reinforce the protein's structure
• Tertiary structure is the overall folding pf a polypeptide chain (3D arrangement of all its amino acid residues)
• Disulfide bonds btw the side chains of cysteine residues in some proteins covalently link regions of proteins -> reduce protein's flexibility & increase stability of tertiary structures
• Quaternary structure : association of 2 or more polypeptides (subunits)
• Collagen is a fibrous protein of 3 polypeptides coiled like a rope
• Hemoglobin is a globular protein consisting of 4 polypeptides : 2 alpha, 2 beta chains
• Transthyretin (TTR) is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine (T4) and retinol binding protein bound to retinal. This is how transthyretin gained its name : transports thyroxine and retinol.
• Supramolecular complexes : act as molecular machines that carry the most complex Cr processes by integrating multiple proteins, each w distinct functions into one large assembly. Ex: transcriptional machine
• 2 general families of chaperones : molecular chaperones and chaperonins
• Molecular chaperones (bind to a short segment of a protein substrate and stabilize unfolded or partly folded proteins -> prevent proteins from aggregating and being degraded (ex : HSP70, HSP90)
• Chaperonins, form a small folding chambers into which all or part of an unfolded protein can be sequestered giving it time and an appropriate environment to fold properly (ex : GroEL)
• bc of mutations or other unidentified reasons -> misfolding which leads to a loss of the normal fct of the protein but often marks it for proteolytic degradation
• If degradation not complete or not keep pace w misfolding -> accumulation of the misfolded protein or its proteolytic fragments contributing to certain degenerative disease characterized by the presence of insoluble, disordered aggregates of twisted-together protein or plaques in various organs, including liver and brain
• Neurodegenerative diseases such as Alzheimer's / Parkinson's disease are marked by the formation of tangled filamentous plaques in a deteriorating brain
• Alzheimer's disease is characterized by the formation of insoluble plaque composed of amyloid proteins that appears as a tangle of filaments at low resolution
• Proteolysis of the naturally occurring amyloid precursor protein yields a short fragment "betta amyloid protein" that for unknown reasons changes from an alpha-helical to beta-sheet conformation. This alternative structure aggregates into the highly stable filaments (amyloid) found in plaques. Similar pathologic changes in other proteins cause other degenerative diseases.
• Sickle-cell disease: change in primary structure

  • Slight change in primary structure can affect a protein's structure and ability to function
  • Sickle-cell disease is an inherited blood disorder that results from a single amino acid substitution in the protein hemoglobin
• Sickle-cell anaemia (SCA) & drepanocytosis is a hereditary blood disorder, characterized by an abnormality in the O-carrying hemoglobin moL in red blood cells -> propensity for the cells to assume an abnormal, rigid, sickle-like shape
• the mol to which a protein binds is "ligand" and in some cases, ligand binding causes a change in the shape of proteins -> regulate protein activity
• ligand specificity : ability of a protein to bind ton one mol or a very small gp of molecules in preference to all other moL
• Ligand affinity : the tightness or strength of binding
• best examples of protein-ligand binding : antibodies binding to antigens
• every antibodies mol of the immunoglobulin igG classes consist of 2 identical heavy & 2 light chains covalently linked by disulfide bonds
• The hand-in-glove fit between ab and the site to which it binds (epitope) on its target ag- in case chicken egg-white lysozyme. The ab contacts the ag w residues from all complementary-determining regions (CDRs)
• Antigen : substance that can elicit a response from a B or T c

  • Usually carried by protein & polysaccharides and less frequently, lipids. This includes parts (coats, capsules, cell wall, flagella, fimbriae & toxins) of bacteria, viruses and other microorganisms
  • Lipids and nucleic acids r ag only when combined w proteins and polysaccharideds

  Exposure to the pathogen activate B & T c w antigen receptors specific for that part of the pathogen
• because each lymphocytes is endowed w a unique receptor and clonally expands in response to an ag -> polyclonal response
• The subset of proteins that catalyze chemical reactions, the making and breaking of cb is called enzymes and enzyme's ligands r called substrates
• Enzyme in a common pathway are often physically associated w one another -> Assembly of enzyme into efficient multienzyme complexes
• 2 roles for proteins degradation

  • 1- degradation removes proteins that r potentially toxic -> improperly folded/assembled or damaged (including the product of mutated genes & proteins damaged by chemically active c metabolites or stress (ex: heat shock)

  • 2- the controlled destruction of normal proteins provides a powerful mechanism for maintaining the appropriate level of the proteins and their activities and for permitting rapid changes in theses levels to help c response to changing conditions
• Eukaryotic c have diff pathway : degradation by enzyme within lysosomes
• Proteasomes r very large protein-degrading macromolecular machines that consist of 50 protein subunits
• C marks proteins that should be degraded by covalently attaching to them a linear chain of multiple copies of a 76-residues polypeptide called ubiquitin
• Ubiquitin : regulatory protein found in almost all tissues of eukaryotic organism (76 amino acids)
• Lysine 48-linked chains are the form of chains that signal proteins to the proteasome which destroys and recycles proteins
• Ubiquitination Post-translational modification where ubiquitin is attached to a substrate protein

  Formed w one the 7 lysine residues from the ubiquitin mol
• The binding of Ca2+ to calmodulin causes a conformational change that permits Ca2+/calmodulin to bind to conserved sequences in various target proteins, thereby switching their activity on or off