Lecture 7 (DNA and Chromosomes) Flashcards
Anfinsen’s Dogma
Protein folding is a spontaneous process in which the protein assumes the conformation of lowest free energy
Protein conformation must be ______, ________, ________
Unique, stable, kinetically accessible
Prions
Infectious, pathological proteins. They adopt rare conformation and stack on top of one another. Some prions are catalytic and cause other “infect” other proteins with misfolding. Alpha to Beta sheet
Kuru
A form of creutzfeldt-Jakob Disease. Characterized by shaking. Discovoered in the Fore people and attributed to their endo-cannabal diet
True or false. Incorrect protein folding leads to many diseases.
True. Accumulation of improperly folded proteins are toxic to the tissue in which they are found. Diseases like Alzheimer’s and huntington’s are caused by incorrect protein folding. Neurodegenerative diseases.
Amyloid plaques are characteristics of what disease?
Alzheimer’s
The energy used by chaperonins while assisting proper protein folding is supplied by?
ATP hydrolysis
Chaperonins
Proteins that provide favorable conditions for the correct folding of other proteins, thus preventing aggregation
Mechanism of action of chaperonins
Undergo conformational changes as a function of the enzymatic hydrolysis of ATP as well as binding by substrates
Where do some molecular chaperones bind in the protein?
They bind to non-polar amino acid side chains.
What is the iterative process of protein folding?
Most popular model of the chaperonin active role. IAM focus on the effect of iterative, and hydrophobic in nature, binding of the protein substrate to the chaperonin. More productive folding by unfolding the protein substrate from misfolded conformations.
What happens when a protein has misfolded more than the allowed number of times?
It is tagged for degradation via the proteasome
Ubiquitin
76 AA “protein” Targets proteins for destruction. The c terminus attaches to lysine side chains of proteins.
E3
The most abundant enzyme related to ubiquitin and protein degradation. It is the ubiquitin ligase.Thought to play a role in substrate recognition
E1
Ubiquitin-activating enzyme. It is dependent on ATP. Modifies Ub so that it is in its reactive state
E2
Ubiquitin conjugating enzyme. These enzymes actually catalyze the attachment of Ub to the substrate protein.
How is Ub attached to proteins?
Through a covalent bond between the cysteine at the C-terminal end of the Ub protein and the lysine side chains of the substrate protein
Ub Conjugation to a substrate depends on what?
ATP being present and hydrolyzed. This forms the covalent bond between Ub and substrate
Polyubiquitylation signals for what?
Proteosomal degradation or DNA repair
Multi-ubiquitylation signals for what?
Endocytosis
Mono-ubiquitylation
Histone regulation
E1 mechanism
Covalent attachmetn of cysteine residue to C-terminal carbonyl of ubiquitin powered by ATP hydrolysis
E2 Mechanism
E2 attaches ubiquitin to epsilon amino group of K residue. Targeted protein then binds to substrate site on E3 ligase.
Does the ubiquitin ligase process happen only once?
No. It can happen many times to form a long poly-ubiquitin chain. The longer the cell, the shorter the life
Which proteasome is the one that participates in protein degradation?
Proteasome 20S
What are chromosomes composed of?
DNA and proteins
What did Fred Griffith’s experiment show?
Experiment involved injecting mice with two strains of virus. It showed that DNA contains the information necessary to give instructions to cells
Avery’s experiment
The molecule that carries heritable information is DNA
Hershey’s Experimenet
isotopes were used to label the capsid and DNA of a virus to determine what bacteriophages leave behind as information in cells. No labeled protein was found, only labeled DNA
What are the precursors of DNA and RNA?
Nucleotides
RNA
AGCU (u instead of T). It’s used as a transient carrier of information.
DNA
AGCT bases. More stable. More equipped to be the molecule for long term storage of the genome
Nucleoside
Nitrogenous base covalently linked to a pentose sugar
Nucleotide
Nitrogenous base linked to a pentose sugar and one phosphate group
How many hydrogen bonds exist between G and C bases
Three
How many hydrogen bonds exist between A and T bases?
Two
How many bases per turn does DNA have?
10
General description of DNA
10 bases per turn
Right handed helix
Has a major and a minor groove which are important recognition sites for motifs of DNA binding proteins
Giemsa Stain
Way to tell chromosome apart. Produces dark regions rich in A-T base pair.
Chromosomes are numbered according to size
Philadelphia Chromosome
A genetic translocation between chromosomes 22 and 9 leads to a fusion chromosome which is very tiny. It expresses BRC-ABL, a constitutive active tyrosine kinase
BRC-ABL
A constitutive active tyrosine kinase. Caused by translocation of genetic material btw two chromosomes.
What did Gleevec start?
Gleevec is a drug therapy that binds to the BRC-ABL enzyme that causes 95% of Leukemia. it marked the dawn of personalized medicine
