Chapter 4 - Tertiary structure Flashcards
The majority of 3D structures are stabilized by ______, but some are stabilized by ______ or coordinated ____ atoms.
numerous weak interactions
covalent disulfide bonds
metal
weak interactions
Hydrogen bonding
electrostatic interaction
Disulfide bonds are formed when:
two nearby cysteine residues are oxidized
____ and ____ are the most
common metal ions in
proteins
Zinc
Iron
First protein structure determined
Myoglobin
Myoglobin
largely α-helical in structure
153 amino acids
4 major classes of structure
- all alpha helices
- all beta sheets
- alpha/beta (intermixed)
- mixed alpha + beta (separate regions)
Fold types:
Four helix bundle fold
Greek key fold
Rossmann fold
TIM barrel fold
FERM domain fold
fold in Heme domain of cytochrome b:
Four helix bundle
Four helix bundle provides ______ for the heme group
hydrophobic pocket
fold in Bacterial CusF copper binding protein
Greek key fold
Fold in bacterial lactate dehydrogenase, with bound
nicotinamide adenine dinucleotide
Rossman fold
Rossman fold is found in:
Proteins that bind nucleotides
TIM Barrel aka:
a/b barrel
TIM barrel found in:
A large number of metabolic
enzymes
Fold found in triose phosphate isomerase
TIM Barrel
FERM domain fold components:
FA: Mostly beta sheets
FB: Only alpha helices
FC: Mostly beta sheets
Quaternary Structure
Polypeptide chains organized in
multiple subunit protein complexes
Homodimer
Simplest quaternary structure
Contains two identical protein subunits
Heterodimer
Contains subunits from different gene products
Quaternary Structures Increase _______
Functionality
Quaternary structure provide:
structural properties not present in individual properties
a mechanism for regulation of protein function through conformational change
Bring linked functional components into close
proximity
Fibrous Proteins
Keratin
Silk
Collagen
Collagen
Primarily found in soft tissues that holds bones together and is the major
constituent of tendons and cartilage.
Multi-subunit complexes that are abundant in
nature
Fibrous proteins
Spherical proteins that consist of multi-subunit protein complexes
Globular proteins
An Example of Globular Proteins
Immunoglobulins
Structure and function are dependent on:
Folding
The free energy difference between the
native (folded) and denatured (unfolded)
must be:
favorable (G < 0)
_____ changes can contribute to the folding
process.
Entropy
Chaperone proteins
Proteins that facilitate the formation of stable 3D
structures
Chaperone fxn:
Help newly synthesized proteins fold properly
Rescue mis-folded proteins
Disrupt protein aggregates
2 types of chaperone protein:
Clamp type (Hsp 70)
Chamber type (GroEL-GroES complex)
Chaperones selectively bind to short stretches of_______ that tend to be exposed in ____ but buried in proteins having a ______ conformation
hydrophobic amino acids
non-native proteins
native
GroEL-GroES has:
seven subunits, 97 residues each.
Tm = 0.5 (50%)
Half of molecules are unfolded
Alzheimers caused by aggregation of:
small Aβ peptides (β-amyloid) causing neuronal death
β-amyloid peptide is released by:
followed by:
the cleavage of amyloid precursor protein by β-secretase
cleavage involving γ-secretase
_____ is then thought to self associate under certain
circumstances to form _____ called _____ in the brain
β-amyloid protein
aggregates
β-amyloid
3 protein folding models:
Hydrophobic collapse
Framework model
Nucleation model
loosely folded tertiary structure
molten globule
______ is necessary since no amino acid side chains can reversibly bind to oxygen.
The Fe2+ -porphyrin
complex
Oxygen only binds to the
prosthetic group with iron in its reduced state (ferrous state)
The Fe2+ -porphyrin complex is called _____ and fxns as a _____
heme
prosthetic group
Myoglobin and hemoglobin are both ______
heme-using oxygen binding proteins
Hemoglobin fxn as
transport of heme bound O2 from lungs and through out circulatory system
Myoglobin fxns as
O2 depot stored in muscle tissue
Two histidine residues are crucial in for O2 binding in globin proteins:
His F7
His F8
His F7
Distal histidine
Hydrogen bound to O2 which is bound to Fe2
Attached to E helix
His F8
Proximal histidine
coordinates to Fe2 directly
Attached to F helix
Oxygenation alters the _____ of the Fe(II)-heme complex
electronic state
the color of hemoglobin in venous blood
dark purple (de oxygenated)
the color of hemoglobin in arterial blood
brilliant scarlet (oxygenated)
These proteins are responsible for the brown color of old meat and dried blood
the Fe(II) becomes oxidized to Fe (III) to form metmyoglobin or methemoglobin
Why is an oxygen carrier such as heme important:
O2 has poor solubility
O2 has poor diffusion through our skin
α1-β1 and α2-β2
Have 35 residues that interact
α1-β2 and α2-β1
Have 19 residues that interact
α-β interactions are mostly:
Hydrophobic, H bonding and ion pairing
In hemoglobin, solvent F channel _____ when O2 is bound
Narrows
How does channel narrow?
α-β complexes shift by 15 degrees in clockwise direction, bring β1-β2 closer together
α -β arrangement in hemoglobin
α2 β1
β2 α1
T state
Tense state
O2 unbound
R state
Relaxed state
O2 is bound
In the T state _____ is ~____ out of the _____
Which is called ______ heme
Fe
0..6 Angstroms
heme plane
Puckered
In R state ___ drags ___ and attached _____
Binding to _____ making heme ____
Fe II
His F8
F helix
O2
planar
Helix F tilta and translates by:
~1 Angstrom
____ are released in T-R transition
Protons
T-R transition requires breakage and reformation of:
many non-covalent interactions between adjacent α -β sub-units
As O2 binds, the other subunits ______, increasing the likelihood of additional O2 binding.
change conformation
Information about the O2-binding status of a heme group is _____ transmitted to the other heme groups by: .
mechanically
motions of the protein
binding of a ligand at one site affects the binding of
another ligand at another site
Allosteric effects
Two models proposed for allosteric effects:
Concerted Model of Allosterism
Sequential Model of Allosterism
Concerted Model of Allosterism
All the subunits must be in either T or R
form, model does not allow combinations
of T and R state
Binding of ligand increases the population of the R state.
Sequential Model of Allosterism
Ligand binding progressively induces
conformational changes in the subunits
greatest changes occurring in
those subunits that have bound ligand.
Protein folding:
G = H - TS
G should be favored (-)
H = (-)
S = (-)
Entropy of water molecules
H2O forms cages around hydrophobic AA, when they get folded, they are free to move around increasing surrounding entropy
