3D Structure of Proteins Flashcards
Peptide Bond
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
Primary Structure
Linear arrangement of amino acid residues
Linked to each other by peptide bonds
N terminus to C terminus
Secondary Structure
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
Antiparallel Beta-sheet
H bonds with one AA
Very stable
Directly lined up
Parallel Beta Sheet
H Bonds with two AA
Not necessarily lined up (caticorner)
Tertiary Structure
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
Quaternary Structure
Subunit arrangement into the complex Subunits are held together by noncovalent associations *Hydrogen Bonds *Salt Bridges *Hydrophobic interactions *Van Der Waals
Collagens Structure
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
Name a globular protein with a hydrophobic center
Myoglobin (to bind oxygen by using a metal in the interior)
Name a globular protein with a hydrophilic center
Porin : acts as a transport protein, but is large enough to allow for passive diffusion making it a sort of channel or “pore”
Denaturing
RNAase use
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’
Levels of Protein Structure
Primary Structure (Straight line) Secondary Structure (Single looping structure) Tertiary Structure (shows 3D turns) Quaternary (Shows fillers and spacing)
Incorrectly folded proteins detected by quality-control mechanism called?
proteasome system
How aggregated proteins differ from normal proteins
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)
How amyloids progress to form amyloid plaques
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
What happens when proteosomes are outmatched!
Autophagosomes take place (deliver contents to lysosomes which break it up)
Protein aggregation and neurodegenerative disease
Seeded polymerization Covalent modification of proteins *Oxidative modification *phosphorylation *ubiquitin-like modifier SUMOylation (small-ubiquitin-like-modifier) *proteolytic cleavage
How do aggregates lead to death of cells which harbor them?
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
Metallochaperones
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)
What characteristic will make a protein more prone to aggregation?
Super oxidized proteins are more prone due to the likelihood of B-sheet formation
SOD1 : what is it…?
Superoxide dismutase (teachers research) Needs metal to function (primarily copper or Cu/Zn) Prevents free radicals!
Infectious Proteins KNOW THIS
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
Molten Globule State (broad view)
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
Molten globule state (in short)
Compact globule with a “molten” side-chain structure that is primarily stabilized by nonspecific hydrophobic interactions.
Calmodulin
Calcium sensor, contains four small units in a single polypeptide chain where each binds its own calcium ion
Context-dependent
Many sequences can change their conformations based on location in different proteins… VDLLKN can be alpha helix or B-strand
METAMORPHIC PROTEINS
Accessory Proteins
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
Chaperons and Chaperonins
Chaperonins are a class of chaperons that work to accomplish the correct folding of proteins Use ATP
