University:
Boston University
Course:
CAS BI 107 | Biology 1
Academic year:

2021
Views:

368

Pages:

13
Author:

oscuroj5dm

Protein Structure Conformational Structure How does the polypeptide chain fold? Protein Structure Conformational Structure How does the polypeptide chain fold? 1) 2) 3) 4) primary structure – sequence of amino acids secondary structure – small units of repetitive structure tertiary structure – overall 3D shape quaternary structure – shape of ≥2 chains 19 4 levels of protein structure In order to understand these levels of structure, you need to understand the nature of the polymer first. In other words, the linkage or PEPTIDE BOND Protein Structure-Secondary The 4 S’s for secondary structure: -dependent on number of amino acids Size Solubility -dependent on AA composition and shape Stability -complex and not well understood Shape Why is there Secondary Structure? 20 Protein Structure-Secondary The Levinthal Paradox (1969): Theoretical calculation: Consider just the a-carbon backbone….. If there are 4 clearly different angles allowed of all the angles at the a-carbon (f and y), then each residue has 2x4=8 degrees of freedom. For a protein of 100 residues, there are 8100 possible conformations to “test” for optimal energetics 8100 = 2 x 1090 different conformations At 1000 billion “tests” per second (1/psec), this is 2 x 1078 seconds to find the best. ⟾ 7 x 1070 years Well …... The age of the universe is 14 x 109 years The shortcut proteins use to fold is the use of 2° structure where most of these degrees of freedom are prescribed by a regular structure. What are these “regular structures?” Secondary Structure 21 Protein Structure-Secondary In the early 1950’s, Linus Pauling and Robert Corey predicted some rules that proteins should follow to find the lowest energy conformation. 1) The peptide bond must be planar without free rotation 2) The degree of H-bonding should be maximized to achieve [consider energetic consequences in the the lowest energy state (unfolded)water ⇌ (folded)water transition] 3) The best H-bonds are linear 4) There should be repeating units of conformation (same) as you go from one residue to the next Using these rules they predicted two basic structures: a-helix b-sheet Protein Structure-Secondary There were no known protein structures until 1957, when Kendrew solved the structure of myoglobin: Imagine the excitement when indeed there were the very helices Pauling predicted! 22 Protein Structure-Secondary The α Helix 1 Right handed Protein Structure-Secondary The α Helix 4 Electrostatics -H-bonds all satisfied (as predicted) -Overall polarity of helix 1 Right handed 100° 2 Dimensions -5 Å diameter -100° rotation/residue -1.5 Å rise/residue -length variable (ave ~45Å (8 residues) 3 Conformational angles - f = – 57° - y = – 47° 23 Protein Structure-Secondary The α Helix d– 1 3 Right handed Conformational angles - f = – 57° - y = – 47° 2 4 Dimensions Electrostatics d+ -5 Å diameter -H-bonds all satisfied -100° rotation/residue (as predicted) -1.5 Å height/residue …..called the “Rise” -Overall polarity of helix -length variable (ave 3.6 residues/turn ~45Å (8 residues) ….called the “Pitch” 5.4 Å/turn Protein Structure-Secondary The α Helix 0 1 3.6 residues per turn (repeat) 2 3 3.6 5.4 Å per turn (repeat) “Pitch” 5 R-groups -all point out, away from the helix 24 Protein Structure-Secondary The α Helix: Space Filling Model Helices can be hydrophobic Helices can be hydrophilic Helices can be mixed: amphipathic Protein Structure-Secondary The α Helix Helices can be mixed: amphipathic LLQSLLSLLQSLLSLLLQW hydrophilic hydrophobic 25 Protein Structure-Secondary The α Helix: Propensities Like: -prefer small, medium, hydrophobic/charged -no steric hindrance at Cb -Glu, Met, Ala, Leu, Lys, Phe, Gln Don’t Like: -Pro -Gly Pro has fixed f = -65° Gly is opposite: has too many degrees of 86 freedom Protein Structure-Secondary The α Helix: other helices Increasing pitch (distance per turn) & rise (distance per residue) à Alpha helices twist 4.116 Repeat units/turn 3.613 3.010 2.27 # of atoms in one turn 26 Protein Structure-Secondary The α Helix: examples Globular Proteins Myoglobin (Mb) Protein Structure-Secondary The α Helix: examples Fibrous Proteins: the a-keratin helix 27 Protein Structure-Secondary The α Helix: examples Fibrous Proteins: the a-keratin helix 5.1 Å per turn (repeat) 3.5 residues per turn (repeat) A Coiled Coil Protein Structure-Secondary The α Helix: examples a-keratin packing Two a-helices are coiled together to make a coiled-coil, which is straight Residues at interface are hydrophobic to stabilize the coiled coil. Residues at interface (pink) must be small to accommodate the packing 28 Protein Structure-Secondary The α Helix: examples Fibrous Proteins: the a-keratin helix a-b-c-d-e-f-g hf hf +/– +/– (L,V,A,G) (E,D,R) b-c-&-f tend to be Ser, Gln, Cys A Coiled Coil Protein Structure-Secondary Notice the >10% Cys Glu a&d e&g ~25-30% ~15-20% b,c,&f ~33% 29 Chemistry of Permanent Waving Protein Structure-Secondary The α Helix: examples Fibrous Proteins: the a-keratin helix One model-in text Hierarchy (small-to-large): a-keratin dimer-coiled-coil Protofilament-two dimers Protofibril-two filaments Microfibril-4 protofibrils (Int. Fil.) 30 Protein Structure-Secondary The α Helix: examples Fibrous Proteins: the a-keratin helix Another model Hierarchy: a-keratin dimer-coiled-coil Protofibril-coiled two dimers (same as Protofilament), Protofibril in other model is 2 protofibrils in this one) Microfibril-8 protofibrils Protein Structure-Secondary d– The α Helix: Summary d+ • Right handed helix • 3.6 aa per turn • 5.4 Å rise per turn • • • • • Carbonyl of residue “n” is H-bonded to NH of n+4 residue Has tightly packed core of main-chain atoms R-groups project outward Has overall macro-dipole (N-term +; C-term –) Can be amphipathic 31

Determination of Primary Structure Protein Structure

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