Biochemistry Wk 4 Flashcards
how many amino acids are there
The 20 amino acids commonly found in proteins are joined together by peptide bonds.
levels of organisation of proteins
primary
secondary
tertiary
quaternary
what is the primary structure
The sequence of amino acids
In proteins, amino acids are joined covalently by peptide bonds, which are amide linkages between the α-carboxyl group of one amino acid and the α- amino group of another.
all amino acid sequences are read from the N- to the C-terminal end
what is a peptide bond
Peptide bonds are resistant to conditions that denature proteins, such as heating and high concentrations of urea
The peptide bond is almost always in the trans configuration , because of steric interference of the R groups when in the cis position.
what is the secondary structure
refers to local folded structures that form within a polypeptide due to interactions between atoms
common: alpha helix and beta pleated sheet- are held by H bonds, which form between the carbonyl O of one amino acid and the amino H of another
what is the alpha helix
It is a rigid, right-handed spiral structure, consisting of a tightly packed, coiled polypeptide backbone core
An α-helix has 3.6 residues per turn, meaning amino acid side chains that are three or four residues apart are bought together in space and so α-helices are stabilized by hydrogen bond formation
Proline disrupts an α-helix because its rigid secondary amino group is not geometrically compatible with the right-handed spiral of the α-helix.
what is a beta sheet
A β-sheet is formed by two or more peptide chains aligned laterally and stabilized by hydrogen bonds between the carboxyl and amino groups of amino acids that either are far apart in a single polypeptide or are in different polypeptide chains
LOOK AT GOODNOTES BOOK
what is the tertiary structure
The tertiary structure of a protein is the pattern of the secondary structural elements folding into a three-dimensional conformation
The three-dimensional structure is flexible and dynamic, with rapidly fluctuating movement in the exact positions of amino acid side chains and domains.
These fluctuating movements take place without unfolding of the protein
The forces that maintain tertiary structure are hydrogen bonds, ionic bonds, van der Waals interactions, the hydrophobic effect, and disulfide bond.
what are Stabilizing interactions-Disulfide bonds
A disulfide bond (–S–S–) is a covalent linkage formed from the sulfhydryl group (−SH) of each of two cysteine residues to produce a cystine residue .
The two cysteines may be separated from each other by many amino acids in the primary sequence of a polypeptide or may even be located on two different polypeptides.
The folding of the polypeptide(s) brings the cysteine residues into proximity and permits covalent bonding of their side chains
A disulfide bond contributes to the stability of the three-dimensional shape of the protein molecule and prevents it from becoming denatured in the extracellular environment.
what are Stabilizing interactions-Hydrophobic bonds
Amino acids with nonpolar side chains tend to be located in the interior of the polypeptide molecule, where they associate with other hydrophobic amino acids.
what are Stabilizing interactions-Hydrogen bonds
Amino acid side chains containing oxygen- or nitrogen-bound hydrogen, such as in the alcohol groups of serine and threonine, can form hydrogen bonds with electron-rich atoms, such as the oxygen of a carboxyl group or carbonyl group of a peptide bond
Formation of hydrogen bonds between polar groups on the surface of proteins and the aqueous solvent enhances the solubility of the protein
what are Stabilizing interactions-Ionic interactions
Negatively charged groups, such as the carboxylate group (−COO−) in the side chain of aspartate or glutamate, can interact with positively charged groups such as the amino group (−NH3+) in the side chain of lysine
what is the quarternary structure
Quaternary structure exists in proteins consisting of two or more identical or different polypeptide chains (subunits).These proteins are called oligomers because they have two or more subunits.
Subunits are held together primarily by noncovalent interactions- hydrogen bonds, ionic bonds, and hydrophobic interactions.
oligomeric proteins can undergo rapid conformational changes that affect biological activity.
what is protein denaturation
Denaturation results in the unfolding and disorganization of a protein’s secondary and tertiary structures without the hydrolysis of peptide bonds.
Denaturing agents include heat, urea, organic solvents, strong acids or bases, detergents, and ions of heavy metals such as lead
what are chaperones in protein folding
Chaperones are proteins that guide proteins along the proper pathways for folding. They protect proteins when they are in the process of folding, shielding them from other proteins that might bind and hinder the process.
Many chaperone proteins are termed “heat shock” proteins because they are made in large amounts when cells are exposed to heat.
names of chaperones
HSP-60 - impressive type of chaperone forms an enclosed environment for folding proteins which totally protects them as they fold.
HSP-70- bind hydrophobic regions of an extended polypeptide and are important in keeping the protein unfolded until its synthesis is completed
what is protein misfolding
Protein folding is a complex process that can sometimes result in improperly folded molecules. These misfolded proteins are usually tagged and degraded within the cell .
intracellular or extracellular aggregates of misfolded proteins can accumulate
Deposits of misfolded proteins are associated with a number of diseases.
what is proteasome-mediated protein turnover
this is mediated by an abundant ATP dependent protease
proteasome acts processively to convert the entire protein substrate into short peptides
proteins destined for degradation are marked by polyubiquitin chains that are added via a multistep conjugation process
what is the ubiquitin proteasome pathway
The ubiquitin (Ub)-proteasome pathway (UPP) of protein degradation. Ub is conjugated to proteins that are destined for degradation by an ATP-dependent process that involves three enzymes.
A chain of five Ub molecules attached to the protein substrate is sufficient for the complex to be recognized by the 26S proteasome. In addition to ATP-dependent reactions, Ub is removed and the protein is linearized and injected into the central core of the proteasome, where it is digested to peptides. The peptides are degraded to amino acids by peptidases in the cytoplasm or used in antigen presentation
potential fates of newly synthesized proteins
correctly folded without any help
correctly folded with help of a molecular chaperone
incompletely folded forms digested by a proteasome
name some amyloid diseases
Misfolding of proteins may occur spontaneously or be caused by a mutation in a particular gene, which then produces an altered protein.
Some apparently normal proteins can, after abnormal proteolytic cleavage, take on a unique conformation that leads to the spontaneous formation of long, fibrillar protein assemblies consisting of β-pleated sheets.
Accumulation of these insoluble fibrous protein aggregates, called amyloids, has been implicated in neurodegenerative disorders such as Parkinson disease and Alzheimer disease (AD)
misfolded protein diseases
AD- amyloid beta and tau protein
Parkinson’s disease- amyloid-beta tau protein alpha-synuclein
mad cow- prions and tau protein
transthyretin amyloidosis- transthyretin
what is AD
Most common cause of dementia in elderly.
Down syndrome patients have increased risk of developing Alzheimer disease, as amyloid precursor protein is located on chromosome 21
more info on AD
The dominant component of the amyloid plaque that accumulates in AD is amyloid β (Aβ), an extracellular peptide containing 40–42 amino acid residues.This peptide, when aggregated in a β-pleated sheet conformation, is neurotoxic.
Mutations to presenilin, the catalytic subunit of γ-secretase, are the most common cause of familial AD
The Aβ that is deposited in the brain in AD is derived by enzymic cleavages from the larger amyloid precursor protein, a single transmembrane protein expressed on the cell surface in the brain and other tissues.
Misfolded protein as the infectious agent in human disease
describe this
The prion protein (PrP) is the causative agent of transmissible spongiform encephalopathies (TSE), including Creutzfeldt-Jakob disease in humans, scrapie in sheep, and bovine spongiform encephalopathy in cattle (popularly called “mad cow” disease)
what is PrPSc
This infectious protein is designated PrPSc.
It is highly resistant to proteolytic degradation and tends to form insoluble aggregates of fibrils.
A noninfectious form of PrPC (C = cellular), encoded by the same gene as the infectious agent, is present in normal mammalian brains on the surface of neurons and glial cells.
The key to becoming infectious apparently lies in changes in the three-dimensional conformation of PrPC.
Research has demonstrated that a number of α- helices present in noninfectious PrPC are replaced by β-sheets in the infectious form
