3D Structure of Proteins

Question 1

Peptide Bond

Answer 1

Formed from the bonding of two amino acids and the release of a water molecule (Carboxyl group releasing O and H2 comes from Amino group)
Proteins go from N to C terminus

Question 2

Primary Structure

Answer 2

Linear arrangement of amino acid residues
Linked to each other by peptide bonds
N terminus to C terminus

Question 3

Secondary Structure

Answer 3

Created by coiling and or pleating of peptide/protein chains
alpha-helices : 5.4A per turn, 1.5A = 1 amino acid…. 3.6 AA per turn … right handed helix more common
B-pleated sheets
B-Turns

Question 4

Antiparallel Beta-sheet

Answer 4

H bonds with one AA
Very stable
Directly lined up

Question 5

Parallel Beta Sheet

Answer 5

H Bonds with two AA

Not necessarily lined up (caticorner)

Question 6

Tertiary Structure

Answer 6

Specific 3D conformation of a particular peptide chain
Most proteins are in globular or spherical conformation
* Hydrophobic interactions
* Disulfide bonds (s-s) : Very common between Cysteines
* Metal Ions
* Hydrogen Bonding

Question 7

Quaternary Structure

Answer 7

Subunit arrangement into the complex 
Subunits are held together by noncovalent associations 
*Hydrogen Bonds
*Salt Bridges
*Hydrophobic interactions 
*Van Der Waals

Question 8

Collagens Structure

Answer 8

Fibrous Proteins (i.e. keratin as well): make tall water-insoluble fibers or sheets (looks like a pillar)
Repeating triplet sequence where every third AA is glycine
20% also is proline or hydroxyproline
Triple Helix (each chain is twisted left) while helix twists to the right

Question 9

Name a globular protein with a hydrophobic center

Answer 9

Myoglobin (to bind oxygen by using a metal in the interior)

Question 10

Name a globular protein with a hydrophilic center

Answer 10

Porin : acts as a transport protein, but is large enough to allow for passive diffusion making it a sort of channel or “pore”

Question 11

Denaturing

RNAase use

Answer 11

Destabilization of proteins by using heat, pH, or changing homeostatic conditions.
RNAase is very efficient at breaking down nucleases, and its on the skin to breakdown virus’

Question 12

Levels of Protein Structure

Answer 12

Primary Structure (Straight line)
Secondary Structure (Single looping structure)
Tertiary Structure (shows 3D turns) 
Quaternary (Shows fillers and spacing)

Question 13

Incorrectly folded proteins detected by quality-control mechanism called?

Answer 13

proteasome system

Question 14

How aggregated proteins differ from normal proteins

Answer 14

Normal has more a-helix structure and little B-strand
Some a-helical structure convert to B-strand, these link together and lead to formation of aggregates
(plaques form from aggregated proteins)

Question 15

How amyloids progress to form amyloid plaques

Answer 15

Seeding (nucleation)
Fibril Formation
Deposit
Characterized by conformational conversion of soluble proteins into insoluble amyloid fibrils (deposited in the heart, liver, spleen, and brain)
*Differ from disease to disease

Question 16

What happens when proteosomes are outmatched!

Answer 16

Autophagosomes take place (deliver contents to lysosomes which break it up)

Question 17

Protein aggregation and neurodegenerative disease

Answer 17

Seeded polymerization 
Covalent modification of proteins
*Oxidative modification
*phosphorylation
*ubiquitin-like modifier SUMOylation (small-ubiquitin-like-modifier)
*proteolytic cleavage

Question 18

How do aggregates lead to death of cells which harbor them?

Answer 18

Controversial answers???
Hypoth: Larger aggregates themselves are not toxic, but smaller ones of the same protein may be the culprits
Causing the cell membrane damages and compromised the integrity of the cell

Question 19

Metallochaperones

Answer 19

Insert correct metal into some metal-containing proteins (1/4 of all proteins require a metal)
Heavy Metals are potent inhibitors of protein folding (Cd, Hg, and Pb)

Question 20

What characteristic will make a protein more prone to aggregation?

Answer 20

Super oxidized proteins are more prone due to the likelihood of B-sheet formation

Question 21

SOD1 : what is it…?

Answer 21

Superoxide dismutase (teachers research)
Needs metal to function (primarily copper or Cu/Zn) 
Prevents free radicals!

Question 22

Infectious Proteins KNOW THIS

Answer 22

Similar to virus in size
Can be transmitted cell-cell (1997 nobel prize)

THREE CHARACTERISTICS OF INFECTIOUS PROTEINS (KNOW)

1) Transmissible agents are the aggregates of specific proteins (prion, a-synuclein, B-amyloid, SOD1)
2) protein aggregates are resistant to dissolving
3) Protein is largely and completely derived from a cellular protein

Question 23

Molten Globule State (broad view)

Answer 23

Presence of a native-like content of secondary structure
Absence of specific tertiary structure
10-30% larger than that of the native state
loosely packed hydrophobic core that increases hydrophobic surface area accessible to solvent

Question 24

Molten globule state (in short)

Answer 24

Compact globule with a “molten” side-chain structure that is primarily stabilized by nonspecific hydrophobic interactions.

Question 25

Calmodulin

Answer 25

Calcium sensor, contains four small units in a single polypeptide chain where each binds its own calcium ion

Question 26

Context-dependent

Answer 26

Many sequences can change their conformations based on location in different proteins… VDLLKN can be alpha helix or B-strand
METAMORPHIC PROTEINS

Question 27

Accessory Proteins

Answer 27

PDI (Protein disulfide isomerases)
PPI (Peptidyl Prolyl cis-trans isomerases)
Molecular chaperones
* HSP 70 (HSP 40) : ATP-driven Reverses misfolds; newly synthesized proteins; unfold/refold of trafficked proteins
* Chaperonins
* HSP 90 (for signal transduction proteins)
* Nucleoplasmins
* Small-HSP (a-crystallin)
- Mitochondria contain their own Hsp60 and Hsp70 that are distinct from those that are found in the cytosol

Question 28

Chaperons and Chaperonins

Answer 28

Chaperonins are a class of chaperons that work to accomplish the correct folding of proteins 
Use ATP