BIO265 Cell Organization (FA24) PDF

Outline for today THE EVOLUTION AND COMPARTMENTALIZATION OF CELLS ENZYMOLOGY 101 ORGANELLES AS BIOCHEMICAL REACTION CENTERS MEMBRANE BOUND AND NON-MEMBRANE BOUND ORGANELLES 1 The origin of the cell How did the first organic molecules f...

Outline for today THE EVOLUTION AND COMPARTMENTALIZATION OF CELLS ENZYMOLOGY 101 ORGANELLES AS BIOCHEMICAL REACTION CENTERS MEMBRANE BOUND AND NON-MEMBRANE BOUND ORGANELLES 1 The origin of the cell How did the first organic molecules form? Stanley Miller (graduate student at the time) – replicated the hypothesized Loading… conditions of ancient earth atmosphere Heat Electricity Variety of organic molecules produced - abiogenesis  Motion : Thermal energy S The origin of the cell Self assembles in aqueous environment The first cell is thought to have arisen through the enclosure of self- replicating RNA by a phospholipid bilayer RNA acts as both an information storage molecule and has enzymatic activity - can direct its own synthesis RNA world hypothesis 4  Key innovations 1. Enclosed phospholipid to modern cells membranes Keep cellular material in Keep non-cellular material out Loading… 5  Key innovations to modern THE CENTRAL DOGMA cells Information 2. Replication and expression of information in genome Necessary for reproduction and evolution Message Product DNA has much greater stability than RNA Alberts 5th 6 Edition  Key innovations to modern cells Early cells – entirely dependent on local 3. Metabolism > - gives energy to replic DNA environment to meet energetic needs ATP – necessary for replication of nucleic acids AND powers biochemical reactions Just remember Cells no longer dependent on 6 y 8 meta. immediate environment for energetic needs produces more doesn't require 82 ATO More efficient ATP generation 7  Evolution of taxonomic kingdoms cyanobacteria proteobacteria Alberts 5th 8 Edition  amba bacteria How did eukaryotes arise? Predatory phagocytosis – the origin of mitochondria? Cooper, 8th Edition Mitochondria and Chloroplasts Have their own membranes Have their own DNA – encode many of their own proteins Undergo fission (replication) somewhat independently in the cell 9 Similarities between bacteria and mitochondria - Circular chromosomes  The typical Prokaryotic cell is DIVA stored Loading… in Alnaimat, Sulaiman & Abushattal, Saqr. (2012). 11 Differences in Prokaryotes and Eukaryotes X ~ ↓ ↑ X - - - ↳ can wrap around protein 12  Prothayotes Organelles are the primary innovation ofPrimary advantages & Gall happens in , cytoplasm Eukaryotes 1. Spatial flow of information ↳ greater regulation of gene protein 2. Concentration/compartmentalization of biochemical reactions Indirect advantages 1. Allows for larger cell sizes 2. Allows for more complex cell morphology Cooper, 8th 13 Edition  Compartmentalization of biochemical reactions - pH of cytoplasm - ~7 pH of lysosome - ~4.5-5.0 pH of mitochondria - ~8.0 Why? pH influences protein folding it changes function If you alter protein , Cooper, 8th 14 Edition Mini Primer 1: Proteins have complex & Dynamic 3D shapes Secondary Structure Tertiary Structure Quaternary Structure I polypeptide G ② Protein structure is dynamic – changes based on environmental conditions, interactions with other proteins, post-translational modifications etc. B 15  reversible Mini Primer 2: Proteins often interact through weak, non-covalent bonds Covalent ex: disulfide bonds 1. Hydrogen bonds 2. Electrostatic interactions 3. Hydrophobic interactions 4. Van der Waals attractions Alberts 5th Edition 16  Amino acid properties impact folding and interactions between proteins Protein folding -> an in inside Hydrophobic Hydrophilic Surface of protein ↓ change function & starture Protein structure informs function!  Biochemical reactions - Enzymology 101 All chemical reactions require energy Enzymes lower the activation energy need for a reaction to proceed Most Enzymes are proteins Enzymes are not modified or destroyed in the reaction - changing conformation changing environmend - Cooper, 8th 19 Edition How do enzymes lower the activation energy? 1. Enzymes bring substrates into close proximity 20 How do enzymes lower the activation energy? 2. Enzymes can facilitate a substrate's confirmational change toward the transition state > induced - Fit 21 How do enzymes lower the activation energy? 3. Enzymes provide safe haven “pockets” (microenvironments) for hydrophobic and ionic interactions 22  Enzyme regulation and phosphorylation activates for much product - inhibitor & to slow down In addition to feedback inhibition and allosteric& regulation, enzymes can be regulated through historting phosphorylation -adding ? structure removing phsophates - This changes protein conformation (shape) and function A Kinases add phosphate groups to proteins - Phosphatases remove phosphate groups Phosphorylation (and other post-translational modifications) can dramatically change structure - The cytoplasm is densely packed & Molecules engage in a “random walk” through the cytoplasm- Brownian motion (thermal) Alberts 5th Edition - Compartmentalization accelerates and increases catalysis rates - Compartmentalization allows cells to establish different and distinct microenvironments https://www.youtube.com/watch? - Compartmentalization greatly increases the v=2fobDHHl11c likelihood of an enzyme “finding” its substrate  Organelles can compartmentalize via membranes > have - DNA but can't live on its own ↳ self-regulated Professor Hyun 26 Lee  The Fluid Mosaic Model In addition to phospholipids, membranes also contain proteins with specialized functions sinside membrane - Integral membrane proteins - Peripheral membrane proteins (temporary) ↳ outside membrane g Transmembrane proteins have hydrophobic residues which span the lipid bilayers Common structures for transmembrane insertion– alpha helix O - 6 (20-25 hydrophobic amino acids if inserted into membrane) Beta barrel  Membranes are semi-permeable ↳ transport : aquaporin purlic - phobics Many organelles are not membrane bound Nucleolus – ribosome production Balbiani body – collection of mitochondria in oocytes S define 5 Loading… Hamdane et al. 2014 PLOS Genetics Butler et al. 2019 Vertebrate Embryogenesis 29 Cells are filled with membrane-less organelles 30 Membrane-less organelles form by liquid- liquid phase separation - exclude other > molecules Li…Rosen, 2012 Nature Li…Rosen 2013 Nature CONDENSATES SELECTIVELY CONCENTRATE =THEY EXCLUDE ‘OTHER’ 31  MOLECULES Membrane-less organelles are dynamic and regulated BINDING/UNBINDING BY ANOTHER MOLECULE MODIFICATIONS ON MOLECULE ABUNDANCE OF MOLECULE CHANGES IN THE ENVIRONMENT : SALT, TEMP, NEARBY STRUCTURES…ETC. 32 Membrane-less organelles usually display liquid-like properties but can form aggregates in a test tube Liquid-like condensate Gel-solid aggregate Louise Jawerth  33 Phase separated proteins are implicated in neurodegenerative diseases Alzheimer’s Parkinson’s Lou Gehrig’s/Amyotrophic Lateral Sclerosis/ALS 34