Introduction to Medical Sciences 1 - Protein Structure PDF

Introduction to Medical Sciences 1 Building Blocks of Cells Part 2 Protein Structure Copyright © Brunel University London v.3 2024. All rights reserved Building Blocks of Cells Dr Ricardo Carnicer Hijazo 2024 Version 3 [email protected] Copyr...

Introduction to Medical Sciences 1 Building Blocks of Cells Part 2 Protein Structure Copyright © Brunel University London v.3 2024. All rights reserved Building Blocks of Cells Dr Ricardo Carnicer Hijazo 2024 Version 3 [email protected] Copyright © Brunel University London v.3 2024. All rights reserved 5  Amino acids Amino acids are the building blocks of all proteins. Their common basic structure contains a central α-carbon atom bound to: An amine group (NH3+) Carboxyl A carboxylic acid group (COO-) Amine group A hydrogen atom (H) α group A variable side chain (R) Variable group Copyright © Brunel University London v.3 2024. All rights reserved 6 Image of the structure of amino acids by Cornell, B. at: http://ib.bioninja.com.au Copyright © Brunel University London v.3 2024. All rights reserved 7 Copyright © Brunel University London v.3 2024. All rights reserved 8  9 Copyright © Brunel University London v.3 2024. All rights reserved Essential amino acid deficiency results in slowed growth in children, decreased immunity, depression, digestive problems, fertility issues, etc. Copyright © Brunel University London v.3 2024. All rights reserved 10 Amino acids can be modified – altering their functions Hydroxyproline (Hyp) - Differs from proline by the presence of a hydroxyl (OH group). - A major component of the protein collagen, comprising ~ 13 %!. - Stabilises collagen structure. - Hyp formation requires vitamin C (ascorbic acid) –a lack of Vit C results in reduced Hyp production and weaker collagen… scurvy! Proline Hydroxyproline H H O H H O H N+ C C O- H N+ C C O- H2C CH2 H2C CH2 CH2 CH Non-polar OH Copyright © Brunel University London v.3 2024. All rights reserved Polar 11 Function of amino acids Protein synthesis Source of Energy Source of Glucose Precursors of other biomolecules (e.g. neurotransmitters) Copyright © Brunel University London v.3 2024. All rights reserved 12 Peptide bond: building proteins Peptide bond formation from Wikimedia Commons Copyright © Brunel University London v.3 2024. All rights reserved 13  Peptide bond: building proteins The peptide will be growing from the N- to the C-terminus. Proteins (polypeptides) have a unique sequence of amino acids. Peptide bond formation from Wikimedia Commons C-terminus N-terminus Copyright © Brunel University London v.3 2024. All rights reserved 14 Protein Folding Protein structural levels created in biorender.com 15 Copyright © Brunel University London v.3 2024. All rights reserved 15 Secondary Structure Secondary structure: Folded structure formed based on the pattern of hydrogen bonds between parts of the same polypeptide chain (α-helix and β-sheet). Hydrogen bond is an attraction between two atoms that already participate in other chemical bonds. One of the atoms is hydrogen, while the other may be any electronegative atom, such as oxygen, chlorine, or fluorine. N Most common type of hydrogen H δ+ bond in proteins involves C=O and N-H groups O δ- C Copyright © Brunel University London v.3 2024. All rights reserved 16 Secondary Structure Alpha Helix Hydrogen bonds in the alpha helix by Theislikerice -CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=108233511 Copyright © Brunel University London v.3 2024. All rights reserved 17 Secondary Structure Alpha Helix - Connective tissue – collagens - DNA binding proteins – transcription factors - Membrane proteins – ion channels, receptors, transporters. Copyright © Brunel University London v.3 2024. All rights reserved 18 Secondary Structure Beta Sheet N H O C 3D animation of a beta sheet by Theislikerice -CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=108233511 Image of a beta sheet by Saylor Academy. Public domain Copyright © Brunel University London v.3 2024. All rights reserved 19 Secondary Structure Examples: Antibodies, cell surface proteins, Beta Sheet enzymes, transport proteins, etc. N H O C Image of a beta sheet by Saylor Academy. Public domain Copyright © Brunel University London v.3 2024. All rights reserved 20 Tertiary Structure Tertiary structure: three-dimensional arrangement of the secondary structure of the polypeptide chain, mainly determined by different types of interaction between amino acid side chains. Proteins are held together through several physical bonds and interactions: - Covalent bonds Disulfide bonds - Non- Hydrogen bonds covalent Ionic interactions interactions Hydrophobic interactions Others Copyright © Brunel University London v.3 2024. All rights reserved 21 Covalent bonds A covalent bond consists of the mutual sharing of one or more pairs of electrons between two atoms. 1. Peptide bond. 2. Disulfide bridges between cysteine residues. Disulfide bond Copyright © Brunel University London v.3 2024. All rights reserved 22 Non-covalent interactions 1. Ionic bond (salt bridge): interaction of two opposite charged side chains. 2. Hydrogen bonding: interaction between the hydrogen atom and an electronegative atom. Ionic Bonding Copyright © Brunel University London v.3 2024. All rights reserved 23 Non-covalent interactions 3. Hydrophobic effect – tendency of non-polar substances to aggregate in an aqueous solution and exclude water molecules. Sequestering the non-polar side chains in the interior of the protein mitigates this ‘hydrophobic effect’. Copyright © Brunel University London v.3 2024. All rights reserved Image showing hydrophobic effect during protein folding by Openlearn 24 Quaternary Structure Quaternary structure is the assembly of multiple polypeptide chains (sub-units) into a complete functional protein unit. Identical proteins Non-identical proteins dimers, trimers etc. distinct peptide chains Chaperonin ATP synthase Copyright © Brunel University London v.3 2024. All rights reserved 25 Quaternary Structure Quaternary structure folding is driven by: - Disulfide bonds. Identical proteins - Hydrophobic interactions. dimers, trimers etc. - Hydrogen bonds. - Salt bridges. ATP synthase Chaperonin Copyright © Brunel University London v.3 2024. All rights reserved 26 Denaturation and Chaperones Denaturation: Disruption of the quaternary, tertiary, and secondary structures of the protein; common causes include changes in pH, temperature, or surrounding chemicals. Denaturation causes unfolding of the protein that will lose its biological activity. Copyright © Brunel University London v.3 2024. All rights reserved 27 Denaturation and Chaperones Denaturation: Disruption of the quaternary, tertiary, and secondary structures of the protein; common causes include changes in pH, temperature, or surrounding chemicals. Denaturation causes unfolding of the protein that will lose its biological activity. Chaperones: Proteins that facilitate the folding of other proteins or rescuing misfolded proteins. Principles of biochemistry. Pearson prentice hall 2006 Unfolded Folded protein protein + + Chaperone 28  Amino-acids Covalent bonding Primary Amino acid sequence Hydrogen bond Secondary Sheets and Helices Disulfide, Hydrogen, Hydrophobic, ionic bonding Tertiary Unique structures Disulfide, Hydrogen, Hydrophobic, ionic bonding Quaternary Interaction of protein subunits 29 29 Copyright © Brunel University London v.3 2024. All rights reserved Clinical relevance of protein folding Many neuro degenerative diseases are associated with misfolded proteins: Alzheimer’s: misfold Tau protein. Parkinson’s: misfold Alpha-synuclein. Creutzfeldt–Jakob disease – infectious prions. Copyright © Brunel University London v.3 2024. All rights reserved 30  Alzheimer’s: misfold Tau protein https://www.youtube.com/watch?v=v5gdH_Hydes Textbook of Biochemistry for Medical Students (DM. Vasudevan) Chapter 3: Proteins Copyright © Brunel University London v.3 2024. All rights reserved Visualising protein structures Protein structures are deposited in the Protein Data Bank (PDB) https://www.rcsb.org/ PyMol is a free and powerful tool to understand protein structure https://pymol.org/2/ Copyright © Brunel University London v.3 2024. All rights reserved 32 To complete this session, please read: Textbook of Biochemistry for medical students 9th Ed. DM Vasudevan Chapter 3, pages 34-39. Copyright © Brunel University London v.3 2024. All rights reserved 33 To contact me: [email protected] Copyright © Brunel University London v.3 2024. All rights reserved