2.04 Proteins Flashcards
Most abundant and functionally diverse molecules in living systems
Proteins
Proteins are linear polymers of _____
Amino acid
Set of all the proteins expressed by an individual cell at a particular time
Proteome
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
Goal is the identification of proteins and of their postranslational modifications whose appearance or disappearance corerelates with physiologic phenomenon, aging, or specific diseases
Proteomics
Building blocks of proteins
Amino acids
Only ____ AA are commonly found in mammalian proteins
20
Except fo proline, each amino acid has
1 carboxyl group
1 amino group
1 unique side chain
_____ dictates the function of the amino acid in a protein
Structure of the R-group
Amino acids with aliphatic side chains
Glycine Alanine Valine Leucine Isoleucine
Amino acids with hydroxylic goups
Serine
Threonine
Tyrosine
Amino acids with side chains containing sulfur atoms
Cysteine
Methionine
Amino acids with aromatic side chains
Histidine
Phenylalanine
Tyrosine
Tryptophan
Imino acid
Proline
AA with side chains containing basic group
Arginine
Lysine
Histidine
AA with acidic groups and their amide
Aspartic acid
Asparagine
Glutamic Acid
Glutamine
AA with nonpolar side chains
Glycine Alanine Valine Leucine Isoleucine Phenylalanine Tryptophan Methionine Proline
Net charge of zero at physiologic pH
Promote hydrophobic interactions
Nonpolar side chains
Nonpolar side chains cluster in the ______ of the protein in __________ and outside of the protein in hydrophilic environment
interior; aqueous solution
Has the smallest side chain
Glycine
Often occurs where peptides bend shaprly
Glycine
First step of heme sythesis
Glycine + Succinyl CoA -> delta-ALA
major inhibitory neurotransmitter in the spinal cord
Glycine
major inhibitory neurotransmitter in the brain
GABA
major excitatory neurotransmitter
Glutamine
used in purine synthesis
Glycine
carries nitrogen from peripheral tissue
Alanine
branched-chain amino acids
Valine, Leucine, Isoleucine
Deficiency in branched chain alphaketoacid dehydrogenase
Maple syrup urine disease
Precursor of tyrosine
Phenylalanine
Deficiency of phenylalanine hydroxylase
Phenylketonuria
Metabolites that accumulate among PKU patients
phenyllactate
phenylacetate
phenylpyruvate
Has the largest side chain
Tryptophan
Tryptophan is the precursor for
Melatonin, Serotonin, Niacin
Transfer of methyl group as S-adenosylmethionine
Methionine
Methionine is precursor for
Homocysteine
Primary cause of myocardial infarction among patients with no known risk factors
Homocysteine
Contributes to the fibrous structure of collagen and interrupts alpha-helices in globular proteins
Proline
Phenylalanine derivatives
Tyrosine>L-dopa>Dopamine>Norepi>Epi
Tyrosine>Thyroxine and Melanin
AA with uncharged polar side chains
Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cysteine
Contains a sulfhydryl group that is an active part of many enzymes
Cysteine
Two cysteines can be connected by a covalent disulfide bond to form
Cystine
Precursor of L-dopa, Thyroxine, Melanin
Tyrosine
Phosphorylation site of enzyme modification
Serine
Serine is often linked to carbohydrate groups in _____
Glycoprotein
Sites for O-linked glycolsylation in Golgi apparatus
Serine, Threonine
Have a carbonyl group and an amide group that can also form hydrogen bonds
Asparagine, Glutamine
Site for N-linked glycosylation in endoplasmic reticulum
Asparagine
Deaminated by glutaminase resulting in the formation of ammonia
Glutamine
Major carrier of nitrogen to the liver from peripheral tissues
Glutamine
Negatively charged at physiologic pH because of the carboxylate group
Acidic side chains
Glutamate is precursor for ______ and _____
GABA, Glutathione
Positively charged because of the amine group
Basic Amino Group
Precursor of histamine
Histidine
Histidine is used in the diagnosis of _______
Folic acid deficiency
Test for folic acid deficiency
N-formiminoglutamate excretion test
Prescursor of creatinine, urea, nitric oxide
Arginine
Found in a handful of proteins, including certain peroxidases and reductases
Selenocysteine
Inserted into polypeptides during translation but is not specified by a simple three-letter codon
Selenocysteine
C
Cysteine
H
Histidine
I
Isoleucine
M
Methionine
S
Serine
V
Valine
A
Alanine
G
Glycine
L
Leucine
P
Proline
T
Threonine
R
Arginine
N
Asparagine
D
Aspartate
E
Glutamate
Q
Glutamine
F
Phenylalanine
Y
Tyrosine
W
Tryptophan
All AA are chiral except for ____
Glycine
Atom in a molecule that is bonded to 4 different chemical species, allowing for optical isomerism
Chiral
Exact mirror images of each other
Stereroisomers/optical isomers/enantiomers
All amino acids in proteins
L-configuration
D-configuration
free D-serine and D-aspartate in ______
D-alanine and D- glutamate in ______
Brain tissue;
Cell walls of gram-positive bacteria
AA that cannot be synthesized by the body and must come from diet
Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginie, Leucine, Lysine
Conditionally Non-essential Amino Acids
Histidine, Arginine
May be made in the body, but usually not enough in growing children
Arginine
May be recycled but should eventually be consumed since it is not made at all
Histidine
In PKU patients, this is considered an essential AA
Tyrosine
Protein structure
Primary
Secondary
Tertiary
Quaternary
Linear sequence of a protein’s AA
Primary Sequence
Attaches alpha-amino group of one AA to the alpha-carbonyl group of another
Peptide bonds
Very stable, can only be disrupted by hydrolysis through prolonged exposure to a strong acid or base at elevated temperatures
Peptide bonds
Folding of short (3-30) contiguous segments of polypeptide into geometrically ordered units
Secondary structure
Regular arrangements of AA that are located near each other in the linear sequence
Secondary structure
Secondary structure is stabilized by excessive
Hydrogen bonding
2 main kinds of secondary structure
alpha helix
beta pleated sheets
Most common
R-handed spiral structure with polypeptide backbone core, with side chains extending outward and H-bonds parallel to spiral
Alpha helix
___ AA per turn of the spiral
3.6
Alpha helix is disrupted by
Proline
Large R-groups (W)
Charged R-groups ()
Surfaces appear flat and pleated
1 or 2 peptide chains parallel to each other
Beta sheet
Beta sheet
Between two polypeptides
Perpendicular interchain H-bonds
Antiparallel
Beta sheet
1 polypeptide
Perpendicular intrachain H bonds
Parallel
Reverses the direction of the polypeptide chain forming a compact and globular shape
beta bends, reverse turn, beta turns
often connect anti parallel beta sheets
composed of 4 AA, with first AA in a hydrogen bond to the fourth AA
beta bends, reverse turns, beta turns
Beta bends
Usually with
Proline and glycine
Stabilized by formation of hydrogen and ionic bonds
beta bends, reverse turns, beta turns
seen in half of an average globular protein
Non-repetitive (loop and coil) structures
Not random, but with less regular structure than alpha helix or beta sheet
Non-repetitive (loop and coil) structures
Many adopt a specific conformation stabilized through H-bond, salt bridge, and hydrophobic interactions with other portions of the protein
Non-repetitive (loop and coil) stuctures
Produced by packing side chains from adjacent secondary structural elements close to each other
Motif
Supersecondary structures
beta-alpha-beta unit
Greek key
beta-meander
beta-barrel
Motif
Supersecondary structures
overall 3 dimensional shape of the protein
Tertiary structure
An axial ratio of <3
globular proteins
An axial ratio of > 10
fibrous proteins
refers to the folding of domains and their final arrangement in the polypeptide
Tertiary structure
Tertiary structure is stabilized by
Disulfide bonds
Hydrophobic interactions
Hydrogen bonds
Ionic bonds
Fundamental structural and functional units of polypeptide
Domain
Combinations of motifs
Domain
structure of protein consisting of more than one polypeptide chain
Quaternary structure
One polypeptide chain
Monomeric
2 polypeptide chains
Dimeric
2 copies of same polypeptide
Homodimer
2 different polypeptide
Heterodimer
Several polypeptides
Oligomeric
Quaternary structure is held together mainly by
Noncovalent bond:
H-bond, Ionic bond, Hydrophobic interactions
Disruption of a protein’s structure
Denaturation
Results in the unfolding and disorganization of the protein’s secondary and tertiary structures, which are not accompanied by hydrolysis of peptide bonds
Reversible under ideal conditions
Denaturation
Means of denaturation
heat organic solvent mechanical mixing strong acids or bases detergents ions of heavy metals like Pb and Hg
Protein folding
Native conformation
thermodynamically favored
Protein folding occurs in
modular or step-wise process
Hydrophobic regions settle in the interior forming
Molten globule
Specialized group of protein required for the proper folding of many species of proteins
Chaperones
Chaperones can also ____ that have become themodynamically trapped in a misfolded dead end by unfolding hydrophobic regions
Rescue proteins
Binds to hydrophic amino acids and shields them from solvent
Hsp70
Provides sheltered environment where polypeptide can fold until all hydrophobic groups are in the interior, preventing aggregation
Hsp60
chaperonins
Facilitate formation of disulfide bonds that stabilizes protein’s native conformation
Protein disulfide isomerase
Catalyzes trans to cis in proline
Proline cis-trans isomerase
Protein folding
More common
In vitro
Protein has already been fully synthesized and will be denatured before allowing primary structure to initiate refolding
In vitro
Has refolding buffer
In vitro
protein denatured and then refolded by biochemical techniques
does not lead to complete unfolding
in vitro
folding happens while protein is being synthesized sequentially in the ribosome
results in intermediate structures
chaperones assist folding
in vivo
cotranslational folding
in vivo
cooperative folding
in vitro
cytosol provides crowded macromolecular environemnt
in vivo
significantly extended in the early stage of protein folding while the protein is being synthesized in the ribosome
in vivo
Fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas, neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells
Prion disease
transmitted through the protein alone and there is no need to change DNA or RNA
Prion disease
Normal protein
Lots of alpha-helices
PrPc
Pathologic conformation, lots of beta-sheets
PrPsc
Characteristic senile plaques and neurofibrillary bundles contain aggregates of the protein-beta amyloid
Alzheimer’s disease
Potential mediator of the conformational translation of beta-amyloid from soluble alpha-helix
Apolipoprotein E
Virtually every life process depends on this class of molecules
Proteins
Optically inactive
Its alpha-carbon has two hydrogen substituents
Glycine
Found in the interior of proteins that function in an aqueous environment and on the surface of proteins that interact with lipids
AA with nonpolar side chains
Found on the outside of proteins that function in an aqueous environment and in the interior of the membrane-associated proteins
AA with uncharged polar side chains/ acidic side chains/ basic side chains
Understanding the _____ structure of proteins is important because many genetic disease result in proteins with abnormal AA sequences, which cause improper folding and loss or impairment of normal function
Primary
Not broken by conditions that denature proteins, such as heating or high concentrations of urea
Peptide bonds
Collagen alpha-chain helix is an example of ______ structure
Secondary
Form of secondary structure in which all of the peptide bond components are involved in hydrogen bonding
Composed of two or more peptide chains
beta sheets
Often connect successive strands of antiparallel beta sheets
Stabilized by the formation of hydrogen and ionic bonds
beta bends
Globular proteins are constructed by combining secondary structural elements (alpha helices, beta sheets, nonrepetitive sequences)
Supersecondary structures
Information needed for correct protein folding is contained in the ____ structure of the polypeptide
Primary
