Lecture 4-Kumar Protein Structure and Function 1

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Peptide Bond Is Rigid and Planar H C C N C O

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Terminology Conformation – spatial arrangement of atoms in a protein Native conformation – conformation of functional protein 5

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8 Alpha Helix

Beta-Sheets Beta-sheets formed from multiple side-by- side beta-strands. Can be in parallel or anti-parallel configuration Anti-parallel beta- sheets more stable 9

10 Bonds holding the tertiary structure of Proteins

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Protein Function Catalysis – enzymes Structural – keratin Transport – hemoglobin Trans-membrane transport – Na+/K+ ATPases Toxins – rattle snake venom, ricin Contractile function – actin, myosin Hormones – insulin Storage Proteins – seeds and eggs Defensive proteins – antibodies 15

Protein Classification One polypeptide chain - monomeric protein More than one - multimeric protein Homomultimer – all one kind of chain Heteromultimer - two or more different chains (e.g. Hemoglobin is a heterotetramer. It has two alpha chains and two beta chains). 16

Protein Classification Fibrous – 1)polypeptides arranged in long strands or sheets 2)water insoluble (lots of hydrophobic AA’s) 3)strong but flexible 4)Structural (keratin, collagen) Globular – 1)polypeptide chains folded into spherical or globular form 2)water soluble 3)contain several types of secondary structure 4)diverse functions (enzymes, regulatory proteins) 17

Protein Classification Simple – composed only of amino acid residues Conjugated – contain prosthetic groups (metal ions, co-factors, lipids, carbohydrates) Example: Hemoglobin – Heme 18

Diseases caused by changes in protein structure spongiform encephalopathy (BSE or mad cow disease) seen in cattle and livestock and Creutzfeldt-Jakob disease (CJD) seen in humans. Sickle Cell Anemia – single amino acid change in hemoglobin related to disease Osteoarthritis – single amino acid change in collagen protein causes joint damage 19

Prion protein misfolding 20 Prion Misfolding

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22 Prion propagation

23 Sickle cell anemia

Mutations in  - or  -globin genes can cause disease state Sickle cell anemia – E6 to V6 Causes V6 to bind to hydrophobic pocket in deoxy-Hb Polymerizes to form long filaments Cause sickling of cells Sickle cell trait offers advantage against malaria Fragile sickle cells can not support parasite 24

Learning objectives-protein structure and function Know the definitions of primary, secondary, tertiary, and quaternary structures or protein Understand the differences between globular and fibrous proteins Know the forces that stabilize these structures Understand the type of bonds that stabilize these structures Understand that certain changes in protein structure can change the structure and function of protein 25