Disulfide Bonds at the Hair Salon Three Alpha Helices Stabilized By Disulfide Bonds! In order for hair to grow 6 inches in one year, 9 1/2 turns of α helix must be produced every second!!! In some proteins, the linear array can Cross link.using cysteine sidechains. A RedOx Reaction to Make or break Disulfide bonds Peptide Bonds A Special Amide bond in proteins How is it made? Also called a dehydration reaction 1
Peptide Bonds( and the neighboring atoms) are planar! Planar Nature of the peptide bonds comes From bonding resonance structures NO FREE ROTATION AROUND THE PEPTIDE BOND (partial double bond character) Bond length implies this double bond character C N = 1.49 Angstroms C=N = 1.27 Angstroms 2
Double bonded atoms can be cis or trans Peptide bonds are almost always trans why? Proline is bad in both orientations. Phi and Psi angles can be used to describe A protein s rotational bonds phi psi 3
Only certain phi and psi angles are possible in most Proteins other angle combinations are impeded by Steric hinderance. Ramachandran plot reveals the most likely Torsional angle combinations. Linus Pauling.a visionary biochemist In 1948, while in bed recovering from a cold, Pauling playfully constructed a crude paper model of a polypeptide chain using the chemical and stereochemical constraints known at that time such as, that the peptide bond was a flat (planar) shape. He concluded that the polypeptide chain was a single stranded helix, which he named the alphahli helix. He won the Nobel prize in chemistry for this in 1954. http://images.google.com/imgres?imgurl=http://www.msu.edu/course/lbs/333/fall/images/pauling.jpg&imgrefurl=http://www.msu.edu/course/lbs/333/fall/pauling.html&h=463&w=298&sz= 73&hl=en&start=11&tbnid=5rdswDdQTEzyaM:&tbnh=128&tbnw=82&prev=/images%3Fq%3DLinus%2BPauling%26ndsp%3D20%26svnum%3D10%26hl%3Den%26rls%3DADBS,ADBS:2006 48,ADBS:en%26sa%3DN Secondary structure Primary structure of proteins Secondary structure of proteins Alpha helix Beta pleated sheet Random coil Hair pin turns (reverse turn) Beta turn 4
Alpha helix Intra strand hydrogen bonding stabilizes Alpha helices Right handed Helix is most Likely.. Supported From the Ramachandran plot 5
Ball and stick representation Ribbon Diagram Cylinder representation Some proteins are dominated by alpha helical structure This is ferritin.can you guess what this protein binds? 6
Another protein structure made from Alpha helices.its called the Coiled coil.. a strong arrangement (like a braided rope) Used in proteins that need to be strong such as structural Proteins (cytoskeletal, hair, blood clots) Beta sheets They are Pleated, with regards to the R groups attached to the amino acids Alternating R groups above and below The plane of the backbone atoms Different R groups on either side 7
Stabilized by Inter strand Hydrogen bonds. Antiparallel beta sheet More stable why? Parallel beta sheet less stable why? Mixed Beta sheet 8
Ball and stick of a twisted Beta sheet Ribbon diagrams of the same Beta sheet Perspectives lets you see the shape. A Beta Barrel protein Fatty acid binding Protein Mostly beta strands 9
Hair pin turn Stabilized By hydrogen Bonding Usually involves proline Random coil (loops) On proteins can be Important Secondary structural Elements.. Like in antibodies This portion in red Interacts with other molecules. Ball and stick of myoglobin Tertiary Structure A combination Of all of the Secondary Structures in a Protein. MOST WATER SOLUBLE PROTEINS HAVE A COMPACT HYDROPHOBIC CORE! 10
The heme prosthetic group. Schematic view Of myoglobin Myoglobin surface charges in space filling models Cross section Porins are inside out. Why? 11
A DNA binding Motif a super secondary structure Proteins can have Domains Quaternary Structure = combinations of tertiary structures subunits A dimer 12
Hemoglobin is tetramer 13
Quaternary Structures form The coats of Most viruses. They self assemble. 4 subunits 60 copies of each = Viral coat! Denaturing agents Destroy Protein 3 D structure RNAse 14
Reduction of the disulfide bond using beta mercaptoethanol Proteins can Refold! 15
Some amino acid sequences can be Found in different secondary structures Stanley Prusiner, Nobel Laureate 1997 Discovered protein based infectious agents Prions Bovine spongiform encephalopathy (mad cow disease) Cruetzfeld Jakob disease Scrapie 16
Similarites Transmissible agent is aggregates of proteins of different molecular weight Protein aggregates are resistant to denaturation Protein is derived from a normal protein found in the brain Protein only Model for Prion diseases. Prions in Action Prion protein Misfolded form Oligomer aggregates protofibrils 17
Amyloid Plaques Protein folding is HIGHLY Cooperative! Half folded Proteins don t seem to exist at least they can be measured 18
Monkey typing Shakespeare s Hamlet If random correct keystrokes Are retained, then it can be done! This is how folding of proteins is Believed to take place so quickly! Local regions form first, then quickly condense Modifications found in some proteins 19
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