1.11_Antibodies_Myosin_2024.pdf

Antibodies - Myosin Lecture 1.13 CHEM 151: Biochemistry I Professor Harrison 1  Antibodies Immunoglobulin Fold W -sheet & IgG 2  Dimer of Heterodimers Vh= variable heavy...

Antibodies - Myosin Lecture 1.13 CHEM 151: Biochemistry I Professor Harrison 1  Antibodies Immunoglobulin Fold W -sheet & IgG 2  Dimer of Heterodimers Vh= variable heavy Vl= variable light H29VY 11gn + Antigen on9in ona in Binding Site 2a + MS Fab binding + oan + /yer CL=constant light Fc CH=constant heavy 3  Hypervariable Loops Confer Specifity to Bind to Antigens (3 from each chain) ·Mount O 4  Bind Many Types of Antigens Other Proteins Small Molecules 5  Dimer of Heterodimers Vh= variable heavy Vl= variable light Antigen Binding Site Fab CL=constant light an + 10012S a t2 mostly ou + vide of ve/18 Fc CH=constant heavy 6 Type Depends on Heavy Chain (only 2 Light Chains -  & ) & Iff. antibodies nor o 7 Different Ig folds have different functions ce11 It binds + 0 8 Protein Engineers are creating designer AB platforms 9 Antibodies are BIG business! 10 Antibodies are BIG business! 11  13 : 00 slide about here drugs not on B cells make antibodies to detect pathogens B cells are activated when they bind antigen and T cells 12 B cell activation 13 Antibody diversity achieved through a two step process: 1) Recombination DNA Exon Rearrangements Alternative Splicing of RNA 14 Step 2) Somatic hypermutation Activation-induced cytidine deaminase (AID) 15 Antibody maturation 16 Activated B cells diversify in the spleen spleen 17  How do Antibodies Help? Precipitate Antigens Apoptosis Cell Death Phagocytosis 18  How new antibodies are made A Polyclonal Antibody represents a collection of antibodies from different B cells monoclonal antibodies come from B cell isolates 19 Antibodies can be engineered using phage display screen 109 protein sequences 20 21 Pros and Cons of poly reactive antibodies 22 23 24 Protein interactions between B-cell and T-cell are critical for signaling eligandam thco 25 26 May 23, 2017 The tissue agnostic approval "for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options," marks yet another milestone for the 27 drug. 28 Chimeric Activated Receptor (CAR) 29 30  Muscle Fiber nurlede Multi 31  Myofibrils Muscle Fiber Components O O proteins 32  Major Components of Myofibrils Thin filament Thick filament G-Actin Polymer (F-actin) Myosin Aggregate 33  Complete Myosin Molecule Tail is a helical coiled coil with 7 residue, non-polar pseudo-repeats (at a & d : a b c d e f g) 34 Single Myosin Head Structure ATP +o move uses 3 Chains: Heavy, ELC, RLC 35  Actin/Myosin Complex proteins contain all forms of 2° structure 5 G-actin 1/2 Myosin Molecule monomers 36  G-Actin Bilobal, globular, binds adenosine nucleotide 37 ATP hydrolysis necessary for polymerization of G-Actin 38 Muscle Contraction/Relaxation My0014 + con + + 9c + 40es1Tp ↓ pulls 39 muscle +y pe 4 Steps in Movement single ATP hydrolysis = single movement binding - weak interactions ATP hydrolysis - conformational change 40 4 Steps in Movement 41 Power Stroke 42  Other Components of Myofibrils: Troponin Complex & Tropomyosin ↳ binds + o 90 + 1n , D100K149 myosin au + 1ve sites 43 Contraction Triggered by Ca2+ Influx in a Muscle Cell 44 Walk-Along mechanism for muscle contraction Watch this video: https://www.youtube.com/watch?v=nTZnBdeIb5c 45 46 47