Biochemistry Wk 4

Question 1

how many amino acids are there

Answer 1

The 20 amino acids commonly found in proteins are joined together by peptide bonds.

Question 2

levels of organisation of proteins

Answer 2

primary
secondary
tertiary
quaternary

Question 3

what is the primary structure

Answer 3

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

Question 4

what is a peptide bond

Answer 4

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.

Question 5

what is the secondary structure

Answer 5

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

Question 6

what is the alpha helix

Answer 6

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.

Question 7

what is a beta sheet

Answer 7

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

Question 8

LOOK AT GOODNOTES BOOK

Question 9

what is the tertiary structure

Answer 9

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.

Question 10

what are Stabilizing interactions-Disulfide bonds

Answer 10

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.

Question 11

what are Stabilizing interactions-Hydrophobic bonds

Answer 11

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.

Question 12

what are Stabilizing interactions-Hydrogen bonds

Answer 12

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

Question 13

what are Stabilizing interactions-Ionic interactions

Answer 13

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

Question 14

what is the quarternary structure

Answer 14

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.

Question 15

what is protein denaturation

Answer 15

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

Question 16

what are chaperones in protein folding

Answer 16

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.

Question 17

names of chaperones

Answer 17

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

Question 18

what is protein misfolding

Answer 18

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.

Question 19

what is proteasome-mediated protein turnover

Answer 19

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

Question 20

what is the ubiquitin proteasome pathway

Answer 20

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

Question 21

potential fates of newly synthesized proteins

Answer 21

correctly folded without any help

correctly folded with help of a molecular chaperone

incompletely folded forms digested by a proteasome

Question 22

name some amyloid diseases

Answer 22

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)

Question 23

misfolded protein diseases

Answer 23

AD- amyloid beta and tau protein
Parkinson’s disease- amyloid-beta tau protein alpha-synuclein

mad cow- prions and tau protein

transthyretin amyloidosis- transthyretin

Question 24

what is AD

Answer 24

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

Question 25

more info on AD

Answer 25

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.

Question 26

Misfolded protein as the infectious agent in human disease

describe this

Answer 26

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)

Question 27

what is PrPSc

Answer 27

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