Proteins: Higher Orders Of Structure Flashcards
What is secondary structure and what are the two common forms?
Secondary Structure refers to a local spatial arrangement of the polypeptide backbone
A-helix
B-Sheet
What is the structure of the a-helix?
Coil held in shape by H-bonds between amide and carbonyl groups of AAs
How does AA sequence affect helix stability?
Small hydrophobic residues are strong helix formers (Ala and Leu)
Proline is a helix breaker
Gly is a helix breaker
Attractive or repulsive interactions between side chains 3-4 AAs apart
Describe the structure of a B-pleated sheet
Polytpeptide chains arranged side by side
Can be parallel or anti parallel in orientation
H-bonds stabilize the chains
What is the difference in H-bonding between B-sheets and a-helixes?
B-sheets: H-bonds are perpendicular to the polypeptide backbone
A-helix - H-bonds are parallel tot he backbone
Describe the structure of B-turns
A 180 degree turn accomplished over 4 amino acids
Pro and gly occur frequently in B-turns
Why are 6% of peptide bonds involving proline in the cis configuration?
These proline residues are mostly involved in B-turns
What is cyclophilin?
A proline isomerase
What is tertiary structure?
The entire three-dimensional conformation of a polypeptide. How secondary structures form domains
What is a domain?
Section of a protein sufficient to perform a particular chemical or physical task.
What forces stabilize a protein’s tertiary structure?
Hydrophobic interactions Hydrophilic interactions Salt Bridges H-bonds Disulfide bonds
What are the pros and cons of using X-Ray Crystallography to determine protein structure?
Pros - no size limits, well-established
Cons-Difficult for membrane proteins, can’t see hydrogen’s
What are the pros and cons of using NMR to determine protein structure?
Pros - no need to crystallize, can see many H’s
Cons - difficult for insoluble proteins, works best for small proteins
What is the Quaternary structure of a protein?
Formed by combination of two or more tertiary subunits.
Stabilized by same forces as tertiary.
What is the role of Chaperons in protein folding?
Responsible for segregating hydrophobic regions of proteins into the interior of the protein.
Name 6 ways proteins can be denatured
Temperature PH Organic Solvents Heavy Metals Chaotropic agents (e.g. detergents/urea) Agitation/whipping
What two residues are post-translationally modified and involved in the inter-molecular cross-linking of collagen?
Lysine and Proline
Modified to hydroxyLys and HydroxyPro
What is the role of prolyl Hydroxylase?
Adds hydroxyl groups to prolyl residues
Facilitates intra-chain H-bonding
What is Lysyl oxidase and what is its role?
A Copper continent Extracellular enzyme that catalyzes the cross-linking of collagen fibrils.
Oxidatively deaminates lysine to Hydroxylysine, forms cross links with other lysine residues.
What is Elastin?
Fibrillar protein found lungs, arteries, elastic ligaments, skin and bladder
What is desmosine and what is its purpose?
Desomsine is a cross-link formed in elastin
Lysyl oxidase catalyzes the formation of this cross-link between three lysine residue side chains.
What is the function and role of a-1 antitrypsin?
Inhibits several proteases including elastase.
Protects from emphysema and COPD.
What proteolytic pathway degrades extracellular and cell surface proteins?
Endosome-Lysosome pathay
What proteolytic pathway degrades cytoplasmic, nucleic, and ER proteins?
Upiquitin-proteasome pathway
What is the axial ratio of fibrous proteins? Globular?
Fibrous - >10
Globular - < 3
Where is fibrillar collagen synthesized in connective tissue? Bone? Cartilage?
Connective - fibroblasts
Bone - Osteoblasts
Cartilage - chondroblats
What four cofactors are required for the prolyl hydroxylase reaction?
A-ketoglutarate
Oxygen
Iron
Ascorbate (Vitamin C)
What happens as a result of ascorbic acid deficiency?
Formation of a stable triple helix is impaired.
Results in Scurvy
-skin discoloration and gum and teeth problems
What is the cause of Menke’s disease?
Copper deficiency, leads to premature birth and nervous system deterioration. Affected individuals usually don’t live past 3
What is Lathyrism and its cause?
Consumption of sweet pea seeds inhibit lysyl oxidase.
Characterized by skeletal and vascular problems
What is Ehlers-Danlos syndrome?
Heterogenous group of connective tissue disorders that result from heritable defects in the metabolism of fibrillar collagen molecules
What is tropoelastin?
The basic soluble unit of Elastin.
