Protein Structure and Foundations Part 2 Flashcards
Forces that stabilize primary structure
Peptide bonds
Forces that stabilize secondary structure
Local hydrogen bonds
Forces that stabilize tertiary structure
Van der Waals, hydrogen bonds, ionic bonds (can be stabilizing or destabilizing depending on charges near each other) hydrophobic interactions, disulfide bonds (list goes from weakest to strongest)
Which force’s drives the formation of tertiary structure and is an entropic process?
Hydrophobic interactions
The geometric arrangement of ALL atoms in a polypeptide. The SUM of the secondary structures making it the sum of all chemical and physical properties of the primary structure.
Tertiary Structure
Why are disulfide bonds important to stabilizing tertiary protein structure?
They are very hard to break. Ex: Proteins in thermal pools use a lot of disulfide bonds because of their strength
Sum of 2 or more tertiary structures - more than 1 polypeptide. May or may not be covalently connected
Quaternary structure
Do individual polypeptides have different conformations when they are alone vs. when they are in multimeric form?
They have different conformations
Multimers or Oligomers
Proteins with a few repeating subunits
What are repeated subunits called?
Protomers
Proteins often have what attached that help them with their function?
Cofactors of Prosthetic Groups
Interacts with proteins through non-covalent means. Binds to enable or help enhance protein’s ability
Cofactors
Group that is covalently attached to enzymes or proteins. Are typically tightly bound to proteins
Prosthetic group
Long, extended rope-like proteins. Mainly to give structure (shape, protection, and integrity). Usually consist of a single type of secondary structure
Fibrous Proteins
Compact/ blobby proteins. Usually for “action” (enzymes, regulators, movers. Huge diversity in these proteins. Often contain several types of secondary structure.
Globular proteins
Why is there a huge diversity in globular proteins?
They have a lot of different jobs and are involved in many different activities.
Fibrous protein involved in hair, wool, nails, claws, quills, horns, hooves, and skin. Repeated secondary structure, strengthened by cross-linking (S-S bonds), and has a lot of hydrophobic regions to promote “packing”
alpha-Keratin
Protein with a different kind of helix (left-handed with 3 strands). Cross linked by unusual covalent bonds. Found in tendons, cartilage, bone, cornea, ECMP
Collagen
Collagen is a tripeptide repeat of Gly-X-Y. (X is often Proline which stabilizes the helical turn. Y is often hydroxyproline). Why does it use Glycine?
It uses glycine because that amino acid is flexible and packs very tightly
Protein named “Fibroin” that has antiparallel Beta-sheets. Has many weak interactions between sheets due to Van der Waals
Silk
Why are Gly and Ala situated between silk Beta-sheets
Fibroin is rich in Ala and Gly. This works out for the structure because of their small or no R groups, they can pack tightly and closer together
Does silk stretch?
Silk does not stretch because the Beta-conformation that it is in is already highly extended.
A globular protein that stores oxygen
myoglobin
A recognizable folding pattern involving 2 or more secondary structure elements (alpha or beta) and the connection between them
motif
Proteins can be organized by their motifs. What are the categories?
All beta, all alpha, alpha + beta (alpha and beta subunits are mostly separate), and alpha/beta (alpha and beta subunits are conjoined/intermingled)
Independently stable and functional part of a protein that can undergo movements as a single entity. Between second and tertiary structure and are separate units of protein structure
Domains
Domains can have entirely different jobs. What are some examples?
Binding molecules like Ca2+, enzymatic activity
Post-translational modifications that can drastically alter a proteins shape
Phosphorylation (adding a phosphate group), glycosylation (attaching sugars), attaching lipids (prenylation)
The final tertiary structure of a protein is (normally) the _ energetic of all possible conformational states that the polypeptide can assume
Least
The name of the state of the fully folded, functional protein
Native state
If a protein is unfolded it is typically _
inactive
Disrupting a folded protein or denaturation is caused by what factors
Change in pH, change in temperature, exposure to different solvents, etc.
Why does a change in pH denature a protein?
Change in pH changes the ionization state of R groups. This can change the electrostatic interactions between R groups which may change shape (repelling or attraction of different groups)
“Helper” proteins that assist other proteins in folding
Molecular Chaperones
Eukaryotic chaperones that use heat
Heat shock proteins (Hsp)
Diseases that arise from a misfiling mechanism. The protein unfolds and becomes insoluble. The insoluble proteins act as a nucleating center for more misfolded proteins. Not infectious
Amyloid Diseases
What do amyloid diseases effect and what are some examples?
They affect different organs like the spleen, kidney, liver, and heart. Examples include Alzheimers, Huntington’s and Parkinson’s
“Infectious” amyloid diseases that often cause holes in brain tissue. Mad cow disease. We don’t know how it gets into the brain yet. Spreads by making other proteins unfold
Prion diseases
How do the hydrophobic interactions that drive tertiary structure work?
They allow the protein to decrease the surface area in folding to reduce the undesirable interactions with water. Most proteins are in a hydrophilic/ water environment so the need for greater entropy makes the proteins fold.
Do most proteins have interactions with other peptides?
Yes. Very few proteins are “lone wolves” and most interact with other peptides essential for their function
Examples of proteins that interact with other peptides/ have different subunits.
Anthrax (2 subunits). Pertussis toxin (5 subunits). Holoenzyme
What would phosphorylation of a protein do to it energetically?
It would give the protein more negative charges which would make it more energetic. This would be due to more repulsion of like charges in the protein
Which amino acids undergo phosphorylation?
Amino acids with OH groups. Thr, Ser, Tyr
How do organic solvents and detergents denature a protein?
They are non-polar so they turn off the hydrophobic interactions which are important for protein folding. This causes the protein to unfold.
Do chaperonins use or create ATP?
They use ATP
The GroEL system is what type of system?
A chaperonin system
Why is the latency period for prion diseases long?
It takes a long time for the unfolded proteins to accumulate. They accumulate very slowly
