5 - Protein Folds and Quaternary Structure Flashcards
What two forces are “fighting” each other in an alpha helix?
Enthalpy (H-bonds, favorable) vs entropy (order, unfavorable)
How many turns are needed to form a stable alpha helix?
3-4 turns
When are beta sheets stable?
When they are packed together (H-bonds)
What is a common phi/psi angle for a beta sheet?
Phi = -140, psi = 130
What is the most common type of beta sheet?
Antiparallel (C and N terminus run in opposite directions in neighboring strands)
Why are antiparallel beta sheets common?
The carbonyl and amide hydrogens line up perfectly to H bond
What types of gaps are found in antiparallel beta sheets?
A large gap and a small gap (alternating)
How come beta sheets are pleated?
The phi and psi angles
What type of twist is seen in an antiparallel beta sheet?
Right handed twist
What is a parallel beta sheet?
C and N terminus run in parallel directions in neighboring strands
Why are parallel beta sheets less common?
The geometry of the H-bonds is not as effective, so it is not as stable
What types of gaps are found in parallel beta sheets?
Even gaps throughout
How come parallel beta sheets are less pleated?
There is a change in side chain orientation, making them less pleated
True or false: a structure can have both parallel and antiparallel beta sheets
True: this is a mixed beta sheet
True or false: all beta sheets are twisted
True: this is important for tertiary structure
What is a beta turn?
Amino acids that facilitate the turn between two beta sheets
What is the most common amino acid for a beta turn and why?
Gly, because a positive phi angle is needed for the beta sheet twist
What is a beta hairpin?
A 2 H-bond anti-parallel adjacent strand connected by a short (2 amino acid) turn
What is the importance of turns in a beta sheet?
There is lots of activity there (glycosylation, etc.)
True or false: a beta sheet can be ampipathic
True: each face could have different properties
How can you determine if a beta sheet is ampipathic?
Every other amino acid defines one face, look for polarity
What is tertiary structure?
A folded protein composed of a collection of secondary structure components
What are some common motifs in tertiary structure?
EF hand, coiled coil, four helix bundle, beta-barrel, TIM barrel, beta-solenoid
In terms of tertiary structure, where are active sites located?
They tend to be located at intersections (loops)
What is a helix loop helix?
Two alpha helices connected by a loop
What do helix interactions usually lead to in tertiary structure?
Align ridges and grooves made by side chains
What does the coiled coil motif use?
Amphipathic alpha helices
What does the beta barrel motif use?
A barrel with beta sheets
What is the structure of a coiled coil motif?
2 alpha helices form an interface together
How do the alpha helices of a coiled coil interact?
They have hydrophobic interactions with one face from each alpha helix
How does the structure of an alpha helix in a coiled coil differ from an alpha helix by itself?
- Coiled coil has 3.5 amino acids per tern (as opposed to 3.6)
- Coiled coil has a heptad repeat
What is a heptad repeat?
A repeating pattern of 7 amino acid residues
What is the advantage of having 3.5 amino acids per turn?
It allows for better registry between repeating groups for good a-d overlap
What is an a-d overlap?
The interactions between the “a” residue on one strand and the “d” residue (4 amino acids away) on another strand in a coiled coil
What is the disadvantage of having 3.5 amino acids per turn?
Lose optimal H-bonding due to changes in geometry (angles)
Why is a coiled coil coiled?
The i+7 residue (8th residue) is tilted for good interface
What is an example of a coiled coil?
Fos Jun
How is a coiled coil used in Fos Jun?
Lock helices together for transcription factor
What is a 4 helix bundle?
4 alpha helices that associate together through hydrophobic interfaces
What types of alpha helices are in 4 helix bundles?
Normal (3.6 amino acids per turn)
What is a helix turn helix?
Two alpha helices connected by a turn
Where are helix turn helix motifs used?
To bind to major groove of DNA
What is an EF hand?
A helix loop helix motif for calcium binding
Where does calcium bind in an EF hand?
In the loop
What is an example of a protein with an EF hand?
Calmodulin
Why does calcium bind in the loop of an EF hand?
Need conformation flexibility to satisfy the rigid metal coordination requirements (specific geometry)
What is a ridge in an alpha helix?
The orientation of the side chains
What is a groove in an alpha helix?
An absence of side chains between two ridges
What is the importance of a ridge and a groove?
Can insert a ridge into a groove for a good packing surface
How does an i, i+4 / i, i+4 ridge packing work?
One helix is tilted 25 degrees, the second starts at 25 degrees and is flipped 180 degrees and then rotated 50 degrees
What is the advantage of fitting a ridge in a groove?
Can screen out water
How does an i, i+3 / i, i+4 ridge packing work?
One helix is tilted 25 degrees, the second starts at -45 degrees, is flipped 180 degrees, and then rotated -20 degrees
What is an i, i+4 ridge?
25 degrees
What is an i, i+3 ridge?
-45 degrees
What is an alpha/beta motif?
A motif with both alpha helices and beta sheets
What is an example of an alpha/beta motif?
A TIM barrel
What is the structure of a TIM barrel?
A beta sheet pore surrounded by alpha helices
What forms the pore in a TIM barrel?
The beta sheets
What forms the core in a TIM barrel?
The alpha helices
What is the schematic of an alpha helix?
A cylinder
What is the schematic of a beta sheet?
An arrow ( N –> C)
What is the TIM barrel motif?
8 pairs of alternating alpha helices and beta sheets (N terminus alpha helix, C terminus beta sheet, 16 elements all together)
What is an example of an enzyme with a TIM barrel?
Triose phosphate isomerase
What is a Rossman fold?
A structure with alternating alpha helices and beta sheets, but with a different topology than a TIM barrel
What is the structure of a Rossman fold?
An open beta sheet structure
What is an example of an enzyme with a Rossman fold?
Lactate dehydrogenase
What is the Rossman fold motif?
6 beta sheets and 4 alpha helices that alternate (N terminus beta sheet, C terminus beta sheet, 2 sets with a crossing loop)
Where is the active site found in a TIM barrel?
On the pore loops (connected helices and sheets)
How come loops are often active sites?
They have great flexibility for chemistry without disrupting the energetics
Where is the active site in a Rossman fold?
At the crevice formed at the switch point
What is a crevice in a Rossman fold?
The place where lots of loops are close together (connecting helices and sheets)
What is a switch point in a Rossman fold?
Goes from one side of the beta sheet to the other
What is an example of a motif with only beta sheets?
A greek key motif
What is the structure of a greek key motif?
Antiparallel beta sheets forming a “stand”
Where is the active site in a greek key?
At the loops at the top of the “stand”
What is the greek key motif?
6 sets of 4 antiparallel beta sheets (last set has both N terminus and C terminus)
What is an example of an enzyme that has a greek key motif?
Neurarimadase in influenza
What is a protein domain?
A portion of a protein that can exist independelty
Where do binding sites frequently occur at?
Domain intersections
What are some characteristics of protein domain intersections?
They are more highly variable, so they can be disrupted without changing the overall structure
