Chp 4 - Protein Structures

Draw out the types of bonds and their qualities

What are the 4 main protein structures, what parts of the amino acid are involved?, and what bonds stabliilze each of them?

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How are Peptide Bonds formed?

Dehydration rxn (H2O produced as a side product)

What is the pKa for a-COOH & a-NH3 WHEN ISNIDE OF A PROTEIN SEQUENCE?

a-COOH → pKa = 3

a-NH3 → pKa = 9

Do mutations have affects?

Yes. Even mutation in one amino acid → can mess up whole protein

What are the two types of secondary structures and what are they connected/stabilized by THE MOST"?

a-helices

B-sheets

• Both stabilized by H-bonds

What are a-helives? How are a-helices stabilized?

• Bonds WITHIN same chain

C=O makes H-bond with a-amino (NH) that is 4 AMINO ACIDS away from it

What are B-sheets? How are B-sheest stabilized? What are the different types?

• Bonds BETWEEN DIFFERENT chains

Parallel, antiparallel, mixed

What are antiparallel chains, how are they set up? ]

[LOCAL] The two chains are lined up in opposite directions

• One chain has NH3 on the left to start

• The other chain has COOh on the left to start

What interactions do antiparallel bave and why are they stronger than parallel

Antiparallel alignment creates straight, short, strong hydroge bonds. Also more H-bonds form, making antiparallel 50% stronger than parallel.

What are parallel chains, how are they set up?

Two chains lined up in same direction

• Both start with NH3 (amino on same side) and run parallel to each other

What interactions do parallel and why are they weaker than antiparallel?

Parallel alignment creates long, angled, weak H-bonds. Less H-bonds form bc of alignment

Which bonds rotate in a peptide? which don’t? Why do the bonds want to rotate?

Peptide bonds → NO rotation

Phi bonds → Rotate

Psi bonds → Rotate

• Bonds want to rotate to have a more stable conformation

What is a phi bond? What’s it between? 

• bond that rotates that is between a-amino and a-carbon

What is a psi bond? What’s it between?

• Bond that roates that is between carbonyl carbon (C-C=O) and alpha carbon

What does the Ramachandram Diagram represent?

Shows steric constraints from atomic size and bond angles for peptides. 

• illustartes which conformations are the most common

What do the blobs and colors of the rachman diagram saying

What interactions are stabilizing tertiary strcuturs? Which bond type stabilizes the most?

3d structures stabilized w/ mainly electrostaic + Disulfide bonds (IF CYSTEINE IS PRESENT)

• Van der Wahls

• Ionic Interactions

• H-bonds

• Disulfide bonds (Covalent0

What is the order of structure for tertiary structures with disulfide bond stabilization w/ electrostatic stabilization. What is the anaology?

TERTIARY Structure

• Domains

  • Motifs

Apartment → Tertiarty structrure

Domain → Rooms within the apartment for their own functions

Motifs → Essential furniture in each specific room for it’s own specific function (ex: oven in kitchen)

WHat are domains? Are they stable independently?

Independent folded stable units within a protein that have their own specific functions

• CAN fold stably on own

What are motifs? Are they stable independently?

The small recurring patterns (made from a-helices and B-sheets) WITHIN a domain that have their own small specific functions

• NOT stable on their own

ARe domains passed throughout evolution

Yes organisms have same domains and have developed and stuck with the same ones

What are examples of Domains that have passed evolutionarly

ATP Binding Domains

Kinase-like folds

DNA-RNA binding domains (helix-turn-helix motifs)

WHat are quaternary structures? What interactions? Two types of proteins?

Multiple protein subunits fold to make big functional complex

• Stabilized w/ noncovalent interactions and maybe some disulfide (if cyestinne)

SUbunits are identical → Homomeric

Subunitis are different → heteromeric

What is the hydrophobic efffect? Why and how does it drive protein folding?

ENTROPY-DRIVEN effect

• Hydrophobic effect drives protein folding b/c water molecules gain entropy when released after trying to come into contact with the hydrophobic amino acids which are packed into the center of a protein

  • Increases the entropy of the system

• Hydrophobic amino acids pack themselves in middle to minimize exposure to water

Makes process energetically facorable (negative ∆G)

What is the levinthal paradox and how does it lead us to know protein folding is not random

If protein folding was random it would take years for protein to be formed

HOw do we know how proteins know what to fold to? What experiment was connected?

Ribonuclease A (protein) exposed to urea (disrupts H-bonds) and B-mercaptoethanol (disrupts disulfide bonds) causing protein to denature → reagents removed → protein folds back into Ribonuclease A

• Protein folding encoded genetically into primary sequence

What does it mean the protein folding is sequence driven? What does it mean?

Means that proteins can be denatured and renatured spontaneously in sollution (outside of the cell)

• Shows that protein folding is ingrained into primary genetic sequence

What is cumaltive Selection? How does it allow for correct stable folding? 

As things rotate, some atoms come closer together. You eventually get stabilization when positive and negative things come together and bind/

• Driven by achieveing lowest possible energy state

  • avorable local interactions are retained, progressively narrowing the conformational search space.

Do you need to consider the ype of amino acid even if they are of the group for specific interactions?

YES-

• Ex: Alanine and leucine. If leucine relaced with alanine in the core of a protein it becomes less stable beacuse leucine is larger and will form more hydrophobic interactions

Clincial Example: What happens if PrPc (a a-helix) comes into contact with prP?

The a-helix PrPc transforms into PrPsc (a B-sheet) and the hydrophobic affects causes the sheets to push together, aggregate, and distrupt cell fun tion

How do you determine Charge of a peptide sequence?

YOU MUST Ignore the a-Amino’s and a-COOH’s because they are forming peptide (amide) bonds between each other → ONLY R groups are considered

REMEMBER TO TAKE INTO ACCOUNT THE N AND C TERMINI