Proteins Dash 3 (Part 2) Flashcards
Experiments have
shown that the final
3D tertiary structure
of a protein ultimately
is determined by the
Primary structure (amino acid sequences)
The 3D fold (shape) of
the protein determines
its .
function
The primary structure of a
protein refers to its
Amino acid sequence
Amino acids in peptides ( — aas) and proteins (typically —- to —– aas) are joined together by peptide bonds (amide bonds) between the carboxyl and amino groups of adjacent amino
acids.
<30 aas
200 to 1,000
Only the R-group side-chains vary. By
convention, protein sequences are
written from left-to-right, from
the proteins ——–
N- to C-terminus.
The average yeast protein
contains how many amino acids?
466
molecular weight of an amino acid is — daltons (Da), the average
molecular weight of a yeast
protein is 52,728 Da. Note that
1 Da = 1 a.m.u. (1 proton mass).
113
refers to short-range, periodic folding
elements that are common in proteins.
Secondary Structure
Secondary structure includes the
a-helix and b sheet and in turns
In the α helix (Fig. 3.4), the backbone
adopts a ——- —– structure
in which there are 3.6 aas per
turn.
Cylindrical spiral
The α helix is stabilized by ??? between backbone carbonyl oxygen and amide nitrogen atoms that are oriented ??? to the helix axis.
H-bonds
parallel
H-bonds occur between residues located in the n and —- positions relative to one another.
n + 4
In β sheets (a.k.a. “???? ???? ”), each β strand adopts an ?????
pleated sheets
Extended conformation
ß strands tend to occur in
pairs or multiple copies in β
sheets that interact with one
another via —— directed
——
to the axis of each
strand.
H-bonds
Perpendicular
Strands can orient ———— or —— to one another in β sheets
Antiparallel or parallel
ß Turns consist of 3-4 amino acids
that form
tight bends
Longer connecting
segments between ß strands are called
Loops
refers to the
folded 3D structure of a protein
Tertiary Structure
Tertiary structure is also known as the —— structure or —— ——-
Native structure or active conformation
Tertiary structure mostly is
stabilized by ——— ——- between secondary structure elements and other internal sequence regions that
cannot be classified as a particular
type of secondary structure.
noncovalent
interactions
The structures of
hundreds of proteins have been
determined by techniques such as
x-ray crystallography and NMR.
are evolutionarily conserved collections of secondary structure elements which have a ——
conformation. They also have a ——- sequence because the aa sequence ultimately determines structure.
Secondary structure motifs
Defined
Consensus
Multisubunit (multimeric)
proteins have another level
of structural organization
known as —— ——-.
Quaternary Structure
refers to the
number of subunits, their
relative positions, and
contacts between the
individual monomers in a
multimeric protein
Quaternary
structure
independently folding and functionally specialized tertiary structure units within a protein.
Domains
The modular domain structure of many proteins has resulted from the ——– and ——- together
of their coding sequences within longer genes.
shuffling and splicing
multimeric proteins
achieve extremely large sizes,
e.g., of subunits
10s-100s
Such complexes exhibit the highest level of structural organization known as
Supramolecular structure
Typically,
supramolecular complexes function
as “——– ——–” in
reference to the fact that the
activities of individual subunits are
coordinated in the performance of
some overall task
macromolecular machines
Through ——- ——- and ——– —– —-
approaches, the sequences
of an enormous number of
proteins have been compiled.
Genome sequencing and classical gene cloning
Proteins that have a common
ancestor are called
Homologs
These —– proteins are composed of mostly α helical
secondary structure
Globular
Comparison of the sequences of the members of protein families has brought to light the fact that amino
acids within a given class
exhibit a large degree of
———- ——-
functional redundancy
Many experiments have shown that
proteins can spontaneously fold
from an unfolded state to their
folded native state
tends to occur via
successive conformational changes
leading to secondary and then
tertiary structure elements
Folding
The ——— conformation of a
protein can be generated by
heating or treatment with certain
organic solvents.
unfolded
(denatured)
The folding of many proteins, particularly large ones, is
kinetically slow and is assisted in ——– by folding agents known as ——-
Vivo
chaperone
Chaperones assist in 1)
folding of ——- polypeptides made by —— , and 2) re-
folding of proteins denatured by ——— ——- such as
heat shock.
nascent polypeptides
Translation
environmental damage,
Molecular chaperones bind to unfolded nascent polypeptide chains as they emerge from the —— ,
and prevent aggregation,
misfolding, and degradation.
ribosome
The hydrolysis of ATP by the chaperone drives conformational
changes that prevent
—— and help drive
——– ——-.
aggregation
protein folding.
Eukaryotic chaperonins such as the —- —— are large
multimeric complexes related to the bacterial GroEL and GroES
proteins.
TriC complex
In neurodegenerative diseases
such as ———- disease and
—– —- disease, insoluble misfolded proteins accumulate in the brain in
pathological lesions known as
——— , resulting in neurodegeneration
plaques
In Alzheimer’s disease, the
protein known as —— ——- protein
is cleaved into a peptide product (β-amyloid) that aggregates and precipitates
in amyloid filaments.
amyloid precursor protein
The misfolding of β-amyloid, which
involves a transition from α
helical to β sheet conformation
leads to ——– ——-
filament formation.
In mad cow disease, ——- proteins
precipitate causing lesions.
Prion
The term —– refers to any molecule that can be bound by a
protein
Ligand
Ligand binding requires ——- complementarity. The
greater the degree of complementarity, the higher the —— and —— of the interaction
molecular
specificity
and affinity
The complementarity-determining regions (CDRs) of
the antibody make highly specific contacts with —— in the
antigen
epitopes
Enzymes are proteins (a few are RNAs called ——-) that catalyze chemical reactions within living organisms.
Ribozymes
In an enzyme-catalyzed reaction, the reactant or what we called a —– ) is converted into the product
Substrate
is
achieved due to the
fact that enzymes are
most complementary to
the transition state
structure formed in
the reaction
Rate enhancement
The transformation of a substrate to the product occurs in the ——- of an
enzyme
Active site
The active site can be subdivided
into a ———— wherein amino acids that catalyze the reaction reside, and a ——– —- that recognizes a specific feature of the substrate, conferring
specificity to the enzyme-substrate
interaction
catalytic site
binding pocket
The French mathematicians —– and —— developed a kinetic
equation to explain the behavior of most enzymes
Michaelis and Menten
They showed that the maximal rate of an enzyme-catalyzed reaction (Vmax) depends on the ——– (Fig. 3.22a) and the
—— —–
for the rate-limiting step of the reaction
concentration of enzyme rate constant
Michaelis and Menten also derived a kinetic constant, the
——- ——
(KM),
Michaelis constant
The lower the KM the higher the —–
of the enzyme for the substrate
Affinity
is the indicative of the affinity of most enzymes for their substrates.
Michaelis Constant (KM)
The KM happens to be the concentration of substrate at which the reaction rate is —– ——.
half-maximal
are enzymes that cleave peptide bonds in other protein
Proteases
The ____ proteases, which are important for digestion and blood coagulation
Serine
Also present are aspartate and
histidine residues that together with serine make up what is
called the
catalytic triad.
The active sites of serine proteases also contain ——- —- that confer specificity by positioning the peptide bond that is to be cleaved next to the
reactive serine
binding pockets
Trypsin-
Chymotrypsin-
Elastase-
basic aas
aromatic aas
small side-chain aa
In the serine protease reaction mechanism, ———– is formed transiently after peptide bond cleavage by serine.
An acyl enzyme intermediate
the rates of pathway
reactions can be increased if
the substrates and products
of each step are —— to
the next enzyme in the
pathway
Channeled
is enhanced in multisubunit enzyme complexes and by attachment of enzymes to scaffolds or even by fusion of encoded enzymes into a single polypeptide chain
Channeling
The proteolytic ——- (——) of proteins is important for regulatory processes, cell renewal, and disposal of denatured and
damaged proteins.
Degradation (turnover)
carry out degradation of endocytosed proteins and retired organelles.
Lysosomes
Cytoplasmic protein degradation
is performed largely by the
molecular machine called the
Proteasome
is a 76-amino-
acid protein that after
conjugation to the protein,
targets it to the proteasome
Ubiquitin
recognize and degrade
ubiquinated proteins
Proteasome
is a very important
messenger in cell signaling
Calcium
ion (Ca2+)
contains 4 helix-loop-helix motifs
(EF hands) each of which can bind
calcium
Calmodulin
Protein function also can be regulated by allosteric transitions
caused by covalent modification via
phosphorylation
typically occurs on serine, threonine, and tyrosine
Phosphorylation
Cells
maintain cytoplasmic calcium
concentration at about .
When calcium concentration rises
above this level due to hormone-
receptor signaling processes, etc.,
it binds to a protein known as
10-7 M
calmodulin
Enzymes known as —— carry out phosphorylation
Kinases
The bindinf of a ligand to a protein typically triggers an ———- (—— —–) conformational change resulting in the modification of its activity.
Allosteric (other shape)
Enzyme catalyzed reactions typically are highly specific, and rate enhancements of
10⁶-10¹²
