Week 3 Biochem notes
Week 3 Biochem notes biology 305
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This 6 page Class Notes was uploaded by Kayla Notetaker on Thursday April 14, 2016. The Class Notes belongs to biology 305 at Northwestern University taught by Professor Unger in Spring 2016. Since its upload, it has received 11 views. For similar materials see Biochemistry in Biology at Northwestern University.
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Date Created: 04/14/16
Week 3 Day 7 Because membranes compartmentalize, there is no way to transfer molecules back and forth without pores The individual types of macromolecules and their simple derivatives will not allow highly diversified pores to develop Need molecules that are not too hydrophilic and no charged backbone Proteins show promise because the backbone is polar and chemistry allows for hydrophobic surfaces and structural diversity Alpha amino acids are the building blocks of proteins Only L-amino acids are used (asymmetry) Memorize nonpolar aliphatic R groups Glycine (G), Alanine (A), Proline (P), Valine (V), Leucine (L), Isoleucine (I), Methionine (M), Serine (S), Threonine (T), Cysteine (C), Asparagine (N), Glutamine (Q) In parenthesis are the single letter name Should also know structures M plays a special role because all protein messages contain M at first position of reading frame P also plays a special role as it mediates many turns in a protein backbone chain C plays a special role because it can form covalent disulfide bonds Memorize aromatic R groups Phenylalanine (F), Tyrosine (Y), Tryptophan (W) W is the largest, rarest, and most hydrophilic Histidine is also aromatic but it is listed with charged sidechains Positively charged R groups Lysine (K), Arginine (R), Histidine (H) Negatively charged R groups Aspartate (D) and Glutamate (E) Backbones Proteins backbone is formed by condensation (loss of H2O) Proteins are linear unbranched polymers The linear sequence of amino acids represent the primary structure of a protein When writing the one letter notation of a protein sequence is written left to right N-terminus always starts sequence because biosynthesis proceeds from N to C terminus If a protein is exposed to water, then it folds up so the hydrophobic parts are away from the water sidechains do not want to be exposed to water, therefore the polypeptide collapses into a blob The initial structure is a straight chain, the secondary structure is helical and laterally packed, the tertiary structure is caused by H-bonds to further stabilize and fold the protein Enthalpy and entropy contribute by the hydrophobic effect because non-polar Energetically the loss of entropy for the backbone and sidechains is offset by the gain of entropy in the solvent So the entropic penalty is offset through hydrogen bonding, ionic interactions, hydrophobic interactions, and sometimes disulfide bridges H-bonding, salt bridges, and hydrophobic contacts are weak interactions Peptide bonds are very stable due to partial delocalization of nitrogen free electron pair The carbonyl oxygen has partial negative charge, the amide nitrogen a partial positive charge which creates a small dipole Pretty much all peptide bonds in proteins occur in trans configuration with few exceptions Peptide bonds are planar because of partial double bond character (C-N is 180 degrees) dihedral angles are key to define backbone configuration (N-C andaC -C) and can in principle adopt any value between -180 and 180 degrees but more constrained due to steric hindrance (but never 0 degrees) Alpha helix P and G break the helix though other amino acids had tendencies to form helices Helices are weak dipoles (positive n terminal and negative C terminal) Residues (R groups) on helix are correlated so that every third and fourth are on the same side Beta sheets Composed on 3+ beta strands All amino acids except P can be part of beta strand The most favorable are V, I, F, Y, W, and T Can form parallel and anti-parallel configurations Beta turns in sheets often contain P and G flexible, disordered stretches of 4 or more residues can replace beta turns DAY 8 Protein folding stabilization Under normal circumstances a protein should always fold into the same native structure Mis-folding does occur but what happens more often is that a chain gets stuck on a local minimum and this requires ATP to correct (chaperones) Copper binding chaperones Some proteins have more than one structurally defined region for binding Typically, a domain contains a specific function A domain is the smallest part of a protein that can adopt a stable fold But some are multidomain proteins Advantages to having domains? Modularity and redundancy (combining development and tuning of protein function) creates new proteins with new functionalities (created by shuffling domains) Protein folds can degenerate aka have different sequences but the same fold but functionally and structurally important residues are always conserved A 30% identical primary structure is guaranteed to have the same fold and big similarities even at 10% Proteins can also form quaternary structures which is an association of 2+ polypeptide chains (chains can be identical or different) What is role of oligomerization Form structural support elements such as actin fibers and microtubules, form pores, increase the local number of catalytic centers/substrate binding sites, form multifunctional protein complexes, enable cooperative behavior, etc Some proteins contain tightly bound non-protein parts such as hemoglobin, metals, phosphate groups, etc and these are particularly prevalent in enzymes Some proteins conjugated with carbohydrates and others to lipids Day 9 Membrane proteins Making of a membrane protein part one Beta barrel needs about 8-12 residues to span a hydrophobic core of a membrane and at least every other sidechain must be hydrophobic to create a closed barrel Alpha helical needs about 20 residues to span hydrophobic core of membrane and every 3 to 4 sidechain is exposed to a lipid and generally must be hydrophobic (additional hydrophobic residues are required to allow helix-helix packing) Helices are self-contained and need no minimum number to achieve stability within the membrane as long as no polar/charged sidechains are exposed within the middle of the membrane core Making of a membrane protein part 2 Beta barrels are severely limited in structural diversity and the function is usually contained within the monomer. They are only found in outer membranes of gram negative bacteria and mitochondria These are hard to predict from their amino acid sequence Alpha helical has no limitations as to what can be built and function is not constrained to the monomer but can be created by oligomerization Most abundant type of membrane protein Transmembrane helices can be predicted from their amino acid sequences (usually) Design of beta barrel proteins part 2 There are 9 rules The number of strands is even and the N and C terminal are at the periplasmic end (the space between the inner cytoplasmic membrane and the bacterial outer membrane) All strands are antiparallel and connected locally to the neighbors along the chain Strand connections at external end are usually long Strand connections at periplasmic end are short Strand tilt is always about 45 degrees and corresponds to sheet twist Surface contacting the nonpolar membrane interior consists of aliphatic sidechains which forms a nonpolar ribbon These aliphatic ribbons are lined by 2 girdles of aromatic side chains Sequence variability of all parts of barrel during evolution is high when compared to soluble proteins External loops show exceptionally high sequence variability and are usually mobile Part 3 ompA are 8 strands with physical linkage between outer membrane and peptidoglycan layer (monomeric) ompF are 16 strands and are diffusion pore for ions and other small molecules (homotrimer) fhuA is 22 strands and does uptake of Fe-siderophore complex, signal transduction (monomer) Design of alpha helical membrane proteins Unlike beta barrels no firm rules have been derived that describe the design because alpha helix is more versatile and the number of functions carried out is much larger Design principles Hydrophobic effect allows incorporation of helix breakers (P, G, T, S, Y, I, V) which creates a larger diversity and can place functional groups within a membrane There is tight helix association Average tilt of transmembrane helix with respect to membrane plane is 21 degrees Disruptions of helical structures Pi-buldge, unwinding, and proline kink they exist to create non- hydrogen bonded carbonyls/amines which interact with ligands or neighboring helices. Proline kinks thought to act as hinges during conformational changes Helical membrane proteins create channels such as Potassium channels, mechanosensitive channels, acetylcholine receptors, These oligomers formed between subunits and positioned along central symmetry axis antiporters, aquaporins, ammonia channels, etc these are monomers with internal duplication in sequence which leads to a structure with pseudo-twofold symmetry in membrane place (left and right look like mirror images) Helical membrane proteins transporters lacY is a pseudo-twofold symmetry substrate and transport occurs along central pore Na+/H+ antiporter and Na/Cl- transporter are monomers that are asymmetric The glutamate transporter is a trimer but substrate transport occurs within each individual monomer Helical membrane proteins enzymes Cytochrome C oxidase is made up of multiple subunits Essentially transmembrane helices create great flexibility in design There is no correlation between appearance and function Association of multiple different membrane proteins can create complex membrane macromolecular machines
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