Protein Structure I
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- What are the degrees of freedom in peptide groups?
-
the alpha-C - C' bond and (psi angle)
the alpha-C - N bond (phi angle) - Why are the degrees of freedom important?
- They allow for protein folding
- What causes secondary structure?
-
The need for the neutralization of the main chain polar groups via H-bonds
This would allow the hydrophobic regions to settle into the interior - What are comp's of secondary s(x)?
-
alpha-helices
beta-sheets
loops - What is the structure of alpha-helix
- peptide backbone w/side chains radiating out
- How is it stabilized?
- by h-bonds btw.C'=0 bond of residue n and the NH residue of n+4
- What is the average length of alpha-helix?
- approx 10 residues = 3 helical turns
- What is almost always observed? R-handed or L-handed alpha-helixes
- R-handed
- What is the net dipole moment for a-helix?
-
partial positive at amino term
partial negative at carbox term - What does this favor?
- bonding of negatively charged groups (phophate)
- Why is proline bad for a-helices?
- side chain bonded to the N = No H-bonding!!!!
- what are the two ways beta strands can interact to form a pleated sheet?
- paralled and anti-parallel
- What characterizes anti-parallel
- narrowly h-bond pairs that alternate w/widely spaced pairs
- What characterizes parallel
- evely spaced h-bonds that bridge the B-strands at an angle
- loop regions are generally at the _______ of the molecule at when exposed to solvent have lots of ________ and ___________ residues
- surface; charged and hydrophilic
- What do loop regions freq. form?
-
binding sites
active sites - What things are the helix-turn-helix motif specific for?
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DNA binding (seen in transcription factors)
Calcium binding - Why does the B-a-B motif exist and what type of B-sheet is it specific to?
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because two adjacent B-sheets must be joined at opposite edges
parallel b-sheet - What is the fundamental unit of tertiary s(x)
- The domain
- What is a domain?
- An area of a polypeptide that can fold independently
- What are the groups of domains
-
1.alpha
2.beta
3.alpha/beta - What is the globin fold
- short a-helices connected by loops; packed together to form a hydrophobic core.
- What are coiled-coils?
- Two right handed a-helices forming a left-handed supercoil
- What are they used for?
- the basis for many fibrous proteins
- How often do the patterns of the side chains repeat?
- Every 7 (Heptad Repeat)
- What compounds contain coiled-coils
- fibrinogen, collectins, RNA/DNA binding proteins, spectrin and dystrophin
- beta-domain structures resemble a?
- barrel
- What is their general s(x)?
- hydrophobic core made up of side of B-strands. surface has loop regions
- What do alpha/beta domains consist of?
-
central parallel or mixed B-sheet;
surrounded by a-helices;
binding crevices formed by loops - What is the s(x) of the TIM barrel
-
twisted parallel b-sheets AND
a-helices connecting opposite sides of the b-sheets - What is the s(x) of the rossman fold?
- open twisted B-sheet surrounded by alpha-helices
- Where is this seen?
- NAD+ binding domain of lactate dehydrogenase
- Where is a leucine-rich motif commonly seen
- at ribonuclease inhibitors
- What 4 interactions stabilize tertiary structure?
-
1.Disulfide bonds
2.Hydrophobic interactions
3.H-bonds
4.Ionic interactions - What are inactive enzymes called?
- zymogens (proenzymes)
- How does N-linked glycosylation work?
- Attachment of oligosacc. group to Asn side chain, ensures proper folding because of recognition by chaperones
- How does 0-linked glycosylation work?
- Attachment of oligosacc. group to either Ser or Thr
- What is the function of carboxyglutamate residues?
-
Binding of Ca++
Inv. in blood clotting and bone structure - What two non-standard A.A.'s are important in the structure of collagen?
- Hydroxyproline, hydroxylysine
- What does scurvy result from?
- Insufficient hydroxyoxylation of collagen due to vit. C defic.
- What are the usual sites for phosphorylation?
-
OH groups of Ser, Thr, and Tyr
sometimes Asp, His, and Lys - What is the function of the acetylation of the amino terminal end of polypeptides?
- Makes them more resistant to degradation
- the formation of disulfide bonds requires an __________ environment
- oxidative
- What is the f(x) of disulfide bonds?
- Stabilize 3-D structure (ex. alpha and beta chains of insulin linked by disulfide bonds)
- Where do cis-proline peptides occur?
- In tight bends of polypeptide chains
- What enzyme catalyzes cis-trans proline isomerization?
- peptidyl prolyl isomerases
- How do lipids tether proteins to the membrane?
- By embedding the hydrophobic portion in the membrane and covalently attaching to the protein via its polar group
- What lipid can attach to the N-terminus?
- Myristoyl group
- What groups attach to the C-terminus?
- phosphatidylinositol and farnesyl
- What A.A. side chain binds palmitoyl groups?
- Cysteine
- What A.A. side chain is sulfonated in a post-translational modification?
- Tyrosine
- Where do disulfide bonds occur in eukaryotic cells? in bacteria?
-
endoplasmic reticulum (rough)
periplasmic space - What side chains are particularly suited for binding metal?
- His, Cys, Asp, Glu
- What are zinc fingers and what is the function of zinc in that structure?
- A class of DNA-transcription factors, zinc stabilizes the DNA-binding region
- What is the structure of myoglobin?
- Single polypep. chain (153 AA's), very compact (primarily alpha-helices),
- What type of AA's are seen in the interior of myoglobin?
- all non-polar residues
- What is the exception for that?
- Two histidines are present inside
- What is the structure of heme?
- protoporphyrin w/a central iron atom
- How does oxygen enter myoglobin given that heme is buried deep inside?
- "rapid molecular flexing" of the amino acid side chains
- What is the structure of hemoglobin?
- Tetrameric; 4 heme groups ass. w/2 alpha-chains and 2 beta-chains
- When 02 binds to hemoglobin what is the result?
- A change in conformation; some ion pairs are broken, some new ones formed
- What is collagen?
- A right-handed superhelix formed by 3 parallel, very extended left-handed helixes.
- What is the common 3-AA sequence?
- Gly-Pro-Hydroxyproline
- What holds the 3 chains together?
- hydrogen bonds btw. proline C=0 and glycine N-H
- What is the purpose of hydroxyproline in collagen?
- Promotes water-mediated H-bonds that stabilize the structure
- What causes osteogenesis imperfecta?
- Substitution of a single larger R-group for Gly in each alpha-chain.
- What largely dictates the folding pattern of proteins?
- the AA sequence
- What is the Cystic Fibrosis Transmembrane Regulator do?
- Ion channel spec. for Cl-
- What causes cystic fibrosis?
- A deletion of Phe at position 508
- At do proteins denature at extreme pH
-
1.Because groups in non-ionized form (such as Met and Tyr) will be able to ionize if they unfold in the extreme pH, so they start the unfolding process
2.Salt bridges are disrupted - How do Urea and Guanidinium denature proteins?
- By breaking inherent H-bonds