University:
Glendale Community College
Course:
BIO160 | Introduction to Human Anatomy and Physiology
Academic year:

2020
Views:

495

Pages:

24
Author:

Kenley Davila

Section 5.2: Peptides §Peptides have biologically important functions §Glutathione is a tripeptide found in most all organisms §Involved in protein and DNA synthesis, toxic substance metabolism, and amino acid transport §Vasopressin is an antidiuretic hormone §Regulates water balance, appetite, and body temperature §Oxytocin is a signal peptide §Aids in uterine contraction §Stimulates ejection of milk by mammary glands Section 5.3: Proteins §Proteins diverse set of functions: §Catalysis (enzymes) §Structure (cell and organismal) §Movement (amoeboid movement) §Defense (antibodies) §Regulation (insulin is a peptide hormone) §Transport (membrane transporters) §Storage (ovalbumin in bird eggs) §Stress Response (heat shock proteins) Section 5.3: Proteins Two main classes: Fibrous, Globular Composition classification Simple – contain only amino acids Conjugated – simple protein with prosthetic grp Levels of structure 1°structure: order of amino acids in a polypeptide chain read from the N-terminal end to the C-terminal end (L to R) 2°structure: arrangement in space of the backbone atoms secondary structures: a-helix and b-pleated sheet 3˚ structure: 3-D arrangement of all atoms including those in the side chains and prosthetic groups Prosthetic groups – atoms other than amino acids Figure 5.14 The Enzyme Adenylate Kinase 4˚ structure: interaction of several polypeptide chains in a multi-subunit protein Section 5.3: Proteins §Primary Structure is the specific amino acid sequence of a protein §Homologous proteins share a similar sequence and arose from the same ancestor gene §Comparing amino acid sequences of a protein between species, those that are identical are invariant and presumed to be essential for function §Primary Structure, Evolution, and Molecular Diseases §Due to evolutionary processes, the amino acid sequence of a protein can change due to alterations in DNA sequences called mutations §Many mutations lead to no change in protein function §Some sequence positions are less stringent (variable) because they perform nonspecific functions §Some changes are said to be conservative, because it is a change to a chemically similar amino acid Section 5.3: Proteins §Mutations can be deleterious, leading to molecular diseases §Sickle cell anemia is caused by a substitution of valine for a glutamic acid in b-globin subunit of hemoglobin §Valine is hydrophobic, unlike the charged glutamic acid §Substitution for hydrophobic valine HbS: molecules aggregate to form sickle-shaped cells §Cells have low oxygen- binding capacity and are susceptible to hemolysis Figure 5.15 Segments of b-chain in HbA and HbS Section 5.3: Proteins §Secondary Structure: -variety of repeating structures §Most common include the a-helix and b-pleated sheet §Stabilized by hydrogen bonding between the carbonyl and the N-H groups of the polypeptide’s backbone Figure 5.17 The a-Helix Figure 5.18 b-Pleated Sheet Section 5.3: Proteins a-helix- rigid, rodlike structure §Coil of the helix is clockwise or right-handed §3.6 amino acids per turn; repeat distance is 5.4Å §Peptide bond is s-trans and planar §C=O of peptide bond is H-bonded to the N-H of 4th amino acid away §C=O----H-N hydrogen bonds are parallel to helical axis §All R groups point outward from helix §Factors that disrupt §Proline creates a bend §Restricted rotation due to its cyclic structure §a-amino group has no N-H for hydrogen bonding §Strong electrostatic repulsion §Lys and Arg or Glu and Asp §Steric repulsion §Val, Ile, Thr Section 5.3: Proteins § b-pleated sheets form when polypeptide chains lie adjacent to one another § Parallel – N terminal to C terminal § Anti-parallel – 1 chain N to C, other C to N § R groups alternate § Above polypeptide chain; next below polypeptide chain § C=O and N-H groups of each peptide bond are perpendicular to axis of the sheet § C=O---H-N hydrogen bonds are between adjacent sheets and perpendicular to the direction of the sheet § Intrachain bonding – chain double back on itself § Interchain bonding – H bonds between 2 different chains Section 5.3: Proteins Figure 5.18 b-Pleated Sheet §Parallel sheets are much less stable than antiparallel sheets Section 5.3: Proteins §Supersecondary structures: the combination of a- and bsections §bab unit: two parallel strands of b-sheet connected by a stretch of a-helix §b-meander: an antiparallel sheet formed by a series of tight reverse turns connecting stretches of a polypeptide chain §aa unit: two antiparallel a-helices §b-barrel: created when b-sheets are extensive enough to fold back on themselves §Greek key: repetitive supersecondary structure formed when an antiparallel sheet doubles back on itself Figure 5.19 Selected Supersecondary Structures Section 5.3: Proteins §Superfamilies are more distantly related proteins (e.g., hemoglobin and myoglobin to neuroglobin) §Proteins are also classified by shape §Globular - proteins which are folded to a more or less spherical shape §Fibrous - contain polypeptide chains organized approximately parallel along a single axis. §Proteins can be classified by composition: §Simple (contain only amino acids) §Conjugated proteins have a protein and nonprotein component (prosthetic group) (i.e., lipoprotein, glycoprotein, or hemoprotein) §Apoprotein – without prosthetic group §Holoprotein – with prosthetic group Section 5.3: Proteins Fibrous Proteins Large amounts of a-helix & bpleated sheets §Contain polypeptide chains organized approximately parallel along a single axis. §Consist of long fibers or large sheets §Tend to be mechanically strong §Insoluble in water and dilute salt solutions §Play important structural roles in nature §Examples are Figure 5.32 a-Keratin §keratin of hair and wool §collagen of connective tissue of animals including cartilage, bones, teeth, skin, and blood vessels Section 5.3: Proteins Globular Proteins Figure 5.35 Heme §Folded to a more or less spherical shape §Tend to be soluble in water and salt solutions §Most polar side chains are on the outside ü interact with the aqueous environment by hydrogen bonding ü ion-dipole interactions §Nonpolar side chains are buried inside §Nearly all have substantial sections of a-helix and b-sheet Section 5.3: Proteins §Myoglobin: found in high concentrations in cardiac and skeletal muscle §Protein component of myoglobin, globin, is a single protein with eight a-helices §Encloses a heme [Fe2+] that has a high affinity for O2 Figure 5.36 Myoglobin Section 5.3: Proteins §Tertiary Structure: 3-dimensional arrangement of atoms in the molecule ü Side chains and prosthetic groups ü Arrangement of helical and pleated-sheet sections §Fibrous protein – much of 3˚ specified by 2˚ structure §Globular protein – 3o structure provides information ü How helical and pleated-sheet sections fold back on each other ü Positions of side-chain atoms & prosthetic groups §Interactions between side chains also plays a role. ü Folding brings widely separated residues into proximity to help stabilize Section 5.3: Proteins Noncovalent interactions §Hydrophobic interactions between non-polar side chains, e.g., Val and Ile §Electrostatic interactions: §Attraction between side chains of opposite charge, e.g., Lys and Glu §Repulsion between side chains of like charge, e.g., Lys and Arg, Glu and Asp §Hydrogen bonding between polar side chains, e.g., Ser and Thr §Hydration shell stabilizes structure Covalent interactions Disulfide (-S-S-) bonds between side chains of cysteines Figure 5.22 Interactions That Maintain Tertiary Structure Section 5.3: Proteins Figure 5.24 Structure of Immunoglobulin G §Quaternary structure: final arrangement for proteins having multiple-subunits §Oligomers: multi-subunit proteins where some or all subunits are identical §Composed of protomers – may contain 1 or more subunits Section 5.3: Proteins Interactions between subunits §Allostery: control of protein function by ligand binding §Allosteric transitions: can change conformation and function §Allosteric effectors or modulators §Positive if increases affinity §Negative if decreases affinity §Hemoglobin and oxygen affinity ü 4 subunits, each with heme group ü Oxygen binding promotes conformation change ü Increasing affinity in other subunits Section 5.3: Proteins §Denaturation: the loss of the structural order (2°, 3°, 4°, or a combination of these) resulting in loss of biological activity §Denaturation conditions 1. Strong acid or base – alter pH, may precipitate 2. Organic solvents – disrupt hydrophobic interactions 3. Detergents – disrupt hydrophobic interactions 4. Reducing agents – disrupts disulfide bridges, hydrogen bonds, hydrophobic interactions 5. Salt concentration – protein aggregation, precipitation 6. Heavy metal ions – changes structure and function 7. Temperature – disrupts hydrogen bonds 8. Mechanical stress – disrupts delicate balance of forces Section 5.3: Proteins §Protein Folding Assistance §Final 3-dimensional conformation comes directly from protein’s primary §Molecular chaperones §Ribosome-Associated chaperones – binds to emerging polypeptide preventing folding until entire polypeptide emerges §Hsp70s – bind and stabilize proteins during the early stages of folding; usually works with co-chaperones §Hsp90s – finalize folding of a limited set of partially unfolded molecules known as client proteins §Chaperonins – increase speed and efficiency of the folding process (Note: Hsp – Heat shock protein) Model of the E. Coli Chaperonin Section 5.3: Proteins Myoglobin §Single polypeptide chain of 153 amino acids §8 regions of a-helix §Single heme group in a hydrophobic pocket §Most polar side chains are on the surface; nonpolar side chains are folded to the interior §Two His side chains are in the interior, involved with interaction with the heme group Section 5.3: Proteins Hemoglobin § § § § A tetramer of two a-chains (141 amino acids each) and two b-chains (153 amino acids each); a2b2 Each chain has 1 heme group § Binds up to 4 molecules of O2 Function of hemoglobin is to transport oxygen Positive cooperativity - binding of O2 increases affinity ü Structure of oxygenated Hb is different from that of unoxygenated Hb Section 5.3: Proteins §Binding of ligands other than oxygen affects hemoglobin’s oxygen-binding properties §pH decrease enhances oxygen release from hemoglobin (Bohr effect) §Waste product CO2 also enhances oxygen release by increasing H+ concentration §Binding of H+ to several ionizable groups on hemoglobin shifts it to its T state §2,3-Bisphosphoglycerate (BPG) is also an important regulator of hemoglobin function §Red blood cells have a high concentration of BPG, which lowers hemoglobin’s affinity for O2 §In the lungs, these processes reverse Section 5.4: Molecular Machines §Molecular Machines §Purposeful movement is a hallmark of living things §This behavior takes a myriad of forms §Biological machines are responsible for these behaviors §Usually ATP or GTP driven §Motor proteins fall into the following categories: 1. Classical motors (myosins, dyneins, and kinesin) 2. Timing devices (EF-Tu in translation) Note: EF-Tu – elongation factor, thermo unstable 3. Microprocessing switching devices (G proteins) Note: transmit signal from outside to inside cell 4. Assembly and disassembly factors (cytoskeleton assembly and disassembly affects cell mechanics)