6. Protein structure II Flashcards
what is tertiary structure
the overall 3D arrangement of all atoms in a polypeptide
describe residue interaction within tertiary structures
residues too far apart to interact in secondary structures may interact here
what holds tertiary structures together
non-covalent interactions: disulfide bonds, hydrogen bonds, ionic bonds
what is quaternary structure
arrangement of multiple polypeptides into a 3D dimensional shape to form a functional protein
T or F: monomers can have quaternary structure
false! only polymers can
define homodimer
polypeptide chains are identical
define heterodimer
polypeptide chains are not identical
what are the 3 key categories of proteins
globular, fibrous, and intrinsically disordered proteins
describe globular proteins
- most enzymes are globular
- these proteins usually contain many secondary structures
describe fibrous proteins
- many structural proteins are fibrous
- contain long strands or sheets
- examples: alpha keratin, collagen, silk fibroin
describe intrinsically disordered proteins
they have no secondary structure at all (either in a section or in the whole thing)
T or F: fibrous proteins have a high level of strength and flexibility
true
what properties allow fibrous proteins to be strong and flexible?
- multiple polypeptides packed into long strands
- insoluble in water (high levels of hydrophobic amino acids)
- all consist of a repeating unit of one secondary structure
in fibrous proteins, why is tertiary structure not distinguishable from secondary structure
they’re fibrous, so folding isn’t really happening
what does a-keratin make up
almost the entire dry weight of hair, wool, nails, claws, quills, horns, and hooves
what type of filament is a-keratin
an intermediate filament
define intermediate filament
cytoskeleton component
T or F: a-keratin is only found in mammals
true
how many helices make up a-keratin
2
what direction are the helices that make up a-keratin
right handed
what do the two helices of a-keratin do
they coil around one another (left handedly) to form a coiled coil that’s strong like a rope
describe the surfaces where the helices of a-keratin touch
the surfaces where they touch are filled with hydrophobic amino acids, interlocking like a zipper
what strengthens the complex quaternary structure of a-keratin
disulfide bonds
what do the coiled-coils combine into
protofilaments
what do protofilaments combine into
protofibrils
how many strands of a-keratin are needed to bind together to make one intermediate filament
32
describe permanent hair treatments
- reducing agents break disulfide bonds connecting the coiled coil
- hair is heated and stretched into desired shape
- oxidizing agent re-establishes the disulfide bonds
- hair has a new shape
what does collagen make up (give examples)
connective tissue is filled with collagen. ie tendons, cartilage, parts of bone
describe the secondary structure of collagen
left handed helix with 3 residues per turn (=a tighter turn than an a-helix)
what amino acids usually make up the turns of collagen helices
glycine, proline, 4-hydroxyproline
what is the entire polypeptide of collagen called
an alpha chain
describe the structure when alpha chains twist around each other
- forms a unique coiled coil
- three left handed helices in the coil form a right handed twist
- glycine projects inwards to the center where they all touch
how much of the protein in your body is collagen
roughly 1/4
what enzyme adds the hydroxyl group to proline to form 4-hydroxyproline
prolyl 3-hydroxylase
what does prolyl 3-hydroxylase require to function
ascorbic acid
what is ascorbic acid known as in humans
vitamin C
what happens when humans have no vitamin C
=no 4-hydroxyproline = improper collagen structure = scurvy
what are the symptoms of scurvy
swollen bleeding gums and teeth falling out, ruptured blood vessels, severe bruising, opening of previously healed scars, swelling and bleeding around joints, hair breakage, anemia
what protein is silk comprised of
fibroin
describe the structure of fibroin
it has extended antiparallel beta sheets with lots of glycine and alanine for tight packing of multiple strands
what stabilizes the beta sheets of silk
extensive hydrogen bonds and optimal van der waals forces
T or F: silk is stretchy
false
T or F: silk is flexible
true; due to many weak interactions
describe the shape/structure of globular proteins
- globs
- much more compact than fibrous proteins b/c they fold back on themselves many times
describe the common characteristics of globular proteins
tightly packed and compact, hydrophobic core, asymmetrical, water soluble
what varied tertiary structures do globular proteins have (2)
motifs and domains
what is another name for a motif
fold or supersecondary structure
what is a motif
a recognizable folding pattern involving two or more elements of secondary structure and the connections between them
what are 2 examples of motifs
beta-alpha-beta loops, beta barrels
T or F: motifs are always independently stable
false; they may or may not be stable
T or F: small motifs can combine into larger motifs
true
give an example of small motifs forming a larger one
the beta strands of multiple b-a-b loops have joined together to form a a-b barrel (in pyruvate kinase)
what is a domain
a part of a polypeptide chain that’s independently stable or could undergo movements as a single entity
up to how many amino acids can a domain be
roughly 400
does each domain have the same function
no, each domain may have a different function
T or F: domains denature when protease cleaves them away from the rest of the protein
false; when this happens, they usually retain their 3D structure
T or F: domains are always isolated from the rest of the protein
false; they may be isolated (forming distinct lobes), but other times there are lots of interdomain interactions
what are helices and strands in a protein often connected by
connected by loops
do the loops that connect helices/strands to the rest of the protein adopt a regular backbone conformation
no, they do not adopt a regular backbone conformation, and they often protrude on the surface of proteins
describe intrinsically disordered proteins
these are protein segments or even entire proteins that lack an ordered structure in solution
why don’t intrinsically disordered proteins have a structure
they lack the large number of hydrophobic residues to drive folding, and are high in proline residues which disrupt possible secondary structures
describe how intrinsically disordered proteins have flexibility that is key to their function
- they tend to have many binding partners
- they can wrap around dif. enzymes to inhibit them
- they can serve as linkers between ordered segments
describe how P53 is disordered
it has a structured central core, but has disordered N and C termini
when does p53 fold, what part folds, and describe what this looks like
the C termini folds when it binds to a ligand. There are 4 possible ligands, and the folded shape is different depending on which ligand is bound
describe quaternary structure, as well as the structure of each protein involved
a protein with more than one polypeptide
each polypeptide within this protein has its own tertiary structure
how are polypeptides in proteins held together
non-covalent interactions
what’s another name for proteins with quaternary structure
multisubunit proteins or multimers
describe the structure of multimers
most of them have identical subunits or repeating groups of non-identical subunits (repeating unit called a protomer)
what symbols are used to refer to non-identical repeating subunits
greek letters
describe the subunits of hemoglobin
has 4 subunits
- alpha subunit and beta subunit form a pair, and there are 2 symmetrical pairs
T or F: protein folding occurs randomly
FALSE; it would take way too long to find the native state this way
describe folding shortcuts
small sections of secondary structures find their final folded form first, which then form localized motifs and then finally longer range interactions
what is proteostasis
it includes all the processes to maintain an active set of properly folded proteins in a cell
what are chaperones
specialized protein complexes that help fold or refold proteins
what happens if a protein is irreversibly misfolded
the cell will have extensive pathways to recycle or degrade it
what is denaturation
the disruption of the native conformation of a protein, leading to loss of function
does denaturation always lead to complete loss of function
no, it can be mild, leading to a partially folded state, or complete unfolding and return to only the primary structure
what causes denaturation
changes in the environment (ie temperature, pH, chemical treatments)
T or F: unfolding of a protein is gradual
false; proteins remain intact until a sudden loss of structure and function. The loss of structure in one part helps destabilize other protein parts
T or F: denaturation is sometimes reversible
true; some proteins will regain completely their native structure and function when the offending condition is removed
describe protein aggregates and how they occur
misfolded proteins will have exposed hydrophobic residues on their surface, and will therefore aggregate and clump together
describe how amyloid fibers are formed
when a protein that is normally secreted from the cell is secreted in it’s misfolded state, and converts into an insoluble amyloid fiber
T or F: amyloid fibers are harmless
FALSE! they’re connected to many diseases ie parkinson’s and alzheimer’s
what are amyloid-caused diseases called
amyloidoses
how do amyloids typically arise? explain their structure
arise from proteins that have some beta sheets when properly folded. Before proper folding is complete, beta sheet regions from one polypeptide associate with sheets from another, and these aggregate into a fibril core with other regions of the protein misfolding around it
what type of residues stabilize the amyloid fibril
aromatic hydrophobic residues
in regards to aromatic residues, what can promote fibril formation
when mutations occur in specific proteins that introduce aromatic residues
is amyloid formation fast or slow
slow; the age on onset is typically 65+
what is PrP
a normal constituent of brain tissue in mammals (role=unknown)
what is the structure of normal PrP (denoted PrPC)
3 alpha helices
what is the second conformation of prp
PrPSc
what is the structure of prpsc
amyloid-like beta sheets
describe the interaction between the two conformations of prp
prpsc converts prpc into prpsc (=domino effect)
how is prpsc damaging
it causes brain degeneration, holes in the brain, and death (=mad cow disease)
what is a prion
proteinaceous infectious particle
describe the early process of viewing atomic structure via xray
- proteins are purified and crystallized
- X ray is pointed at the crystal, the beam diffracts onto a photographic film
- the diffraction patterns lead to an electron density map
what does the electron density map allow us to see
allows the determination of the position of each nucleus in the crystal. We can then use computers to generate 3D structures
what was the purpose of crystallizing the protein for viewing
hopefully each individual protein is fixed in the same orientation
describe cryo-electron microscopy
used to determine protein structure
- protein was frozen and purified, and then observed under the EM
why is cryo-EM better than xray crystallography
cryo-EM can visualize large and dynamic proteins, while the other cannot
