protein structure and folding some facts and fundamental conepts cherri hsu 02-2789-8658 institute...
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Protein structure and folding
Some facts and fundamental conepts
Cherri Hsu
02-2789-8658
Institute of Chemistry B307
Goals and plans Understand basic facts of protein structures. Understand general concepts that determines
structure and dynamics. Physics Evolution
Go through Chapters 8 and 9 of V&V book. A few more stories I’ve learned. My own review in protein folding prediction and
simulation.
Structural basis:
Hierarchy of protein structures Primary: sequence Secondary: local structures Tertiary: 3-dimension structure of a peptide chain. Quaternary: assembly of protein subunits (multiple
chains) Local structural characteristics:
- angles; Ramachandran plots. -Helixes -Sheets Loops
Methods for determing protein structures
X-ray diffraction
NMR
Determining molecular structures
Method Uses Limits
Infrared Absorption
Assigning local bonding types and structures
Small organic molecules.
NMRAssigning local bonding types and structures; Measuring distances
Small molecules
Small proteins (< 40 kDa?)
X-ray diffraction
Atomic resolution of molecular structures
Virtually no limit over the sizes of the molecules. Single crystals needed.
Electron microscopy & 2-D diffraction
Good for large proteins. No crystals needed.
Large, low resolution structures.
IR (Absorption) Spectra
3000 2000 1000Wavenumber (cm-1)
0.0
0.5
1.0
Transmittance
1030.49
1385.89
1412.02
1449.48
2831.01
2944.26
3327.53
3646.35
3000 2000 1000Wavenumber (cm-1)
0.0
0.5
1.0
Transmittance
428.61
804.7
879.57
1044.11
1085.9
1320.08
1381.02
1448.06
1924.26
2883.64
2974.18
3310.22
3315.44
3342.43
3356.36
3634.95
3000 2000 1000Wavenumber (cm-1)
0.0
0.5
1.0
Transmittance
937.8 1
103.03
1116.14
1166.85
1177.34
1191.33
1453.6
1462.34
2047.21
2118.9
2818.3
2831.41
2887.36
2922.33
2980.03
2995.77
Methanol: CH3OH
Ethanol:C2H5OHC2H6O
Methyl ether:CH3OCH3
C2H6O
Nuclear Magnetic Resonance
NMR is an important tool in chemistry
QuickTime™ and aTIFF (LZW) decompressor
are needed to see this picture.
2D NMR?
A table that lists different 2D NMR techniques.
Can be used to determine distance between atoms.
Will be further introduced in next semester.
X-ray diffraction
X-ray diffraction:Physics2000: wave Physics2000: two slits
http://www.ysbl.york.ac.uk/~cowtan/fourier/fourier.html
Basic building blocks of protein structures
Are proteins sticky tapes?
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Figure 8-1 The trans-peptide group.
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Figure 8-2 The cis-peptide group.
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“trans” is more stable “cis” conformation is
rarely seen. For the peptide
bonds follow proline residue, ~10% are “cis”.
Fibrous proteins
Keratin
A mechanically durable, chemically unreactive protein.
-keratin occur in mammals (hair) -keratin occur in birds (feather) and
reptiles.
-Keratin From x-ray, structure expected: -helix But, the pitch is 5.1Å, rather than normal 5.4 Å. Coiled coil is expected. Rich in Cys residues, form disulfide bonds and cross-
link adjacent peptide chains. “hard” or “soft” : high or low in sulfur content. Hard: hair, horn, nail Soft: skin
When disulfide bonds cleaved, an -keratin can be streched to become a -pleated sheet.
-Keratin From x-ray, structure expected: -helix But, pitch is 5.1Å, rather than normal 5.4 Å. Coiled coil is expected. Rich in Cys residues, form disulfide bonds and
cross-link adjacent peptide chains. “hard” or “soft” : high or low in sulfur content. Hard: hair, horn, nail Soft: skin
When disulfide bonds cleaved, an -keratin can be streched to become a -pleated sheet.
Collagen
Occurs virtually in every tissue. Connective tissues. Mammals have at least 33 genetically
distinct polypeptide chains. 20 distinct collagen types in different tissues.
Hyp: A special residue found in collagens
Collagen Nearly 1/3 of its residues are Gly. 15-30% are Hyp residues. Hyp are converted to Hyp after collagen
polypeptides are synthesized. The conversion is through prolyl hudroxylase,
and it requires Ascorbic acid (vit. C). Hyp offers extra H-bondings. (possibly to
peptides and to water)
Globular proteins
Enzymes
Transport and receptor proteins
Soluable proteins
Membrane proteins
Physical forces determining protein structures
H-bonding
Electro-static interactions
Hydrophobic forces
H-bonds
D-H … A Assignment: if D…A < 3.7 Å in crystal
structure. (normally 2.7-3.1 Å). Energy of stablization: -12~-40 kJ/mol) Tends to be linear. Only weakly stabilize proteins. (!?)
A survey over H-bonds in globular proteins (J. Mol. Biol. (1992) 226, 1143)
Most H-bonds are local.
Most H-bonds are between beckbone atoms.