Protein Structure and classification.pptx

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1. Protein Structure The 20 amino acids are joined together by peptide bonds. The linear sequence contains the information necessary to generate a protein molecule with a unique three-dimensional shape. The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels, namely, primary, secondary, tertiary, and quaternary

2. Primary structure The sequence of amino acids in a protein The AA sequence must be written from the N-terminus to the C-terminus . Many genetic diseases result in proteins with abnormal amino acid sequences, (Sickle cell anemia, Glu replaced with Val)

3. Peptide bond Peptide bonds are responsible for maintaining the primary structure Linkage of many amino acids through peptide bonds results in an unbranched chain called a polypeptide

4. Primary structure of insulin Two peptides of 21 and 30 AAs Two inter-chain -S-S- bonds One intra-chain -S-S- bond

5. SECONDARY STRUCTURE OF PROTEINS Regular arrangements of amino acids that are located near to each other in the linear sequence . The R group has an impact on the likelihood of secondary structure formation The α-helix, β-sheet, and β-bend (β-turn) are examples of secondary structures

6. α helix A spiral structure, consisting of a tightly packed, coiled polypeptide backbone core, α- helix can turn right or left from N to C terminus – only right-handed are observed in nature There are 3.6 residues per turn Diverse Gp of Proteins, i-e Keratins (fibrous proteins) and myoglobin(globular, flexible molecule

7. β-pleated sheet An extended zigzag conformation of protein backbones Protein backbones are arranged side-by-side through H-bonds . H-bonds are perpendicular to the backbone direction. The side chains of adjacent AAs protrude in opposite directions . The adjacent protein backbones can be either parallel or anti-parallel .

8. β-turn One β-turn involves four AAs. The -CO and -NH groups of the first AA are hydrogen bonded to the -NH and -CO groups of the fourth AA , respectively. The β-turn reverses abruptly the direction of a protein backbone. H-bonds are perpendicular to the protein backbone.

9. β-turn

10. Non repetitive secondary structure Approximately one half of globular protein -organized into repetitive structures, such as the α-helix and/or β-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These non repetitive secondary structures are not “random,” but rather simply have a less regular structure

11. Some common structural motifs combining α-helices and/or β-sheets

12. Supersecondary structures (motifs) Globular proteins are constructed by combining secondary structural elements (α-helices, β-sheets, non repetitive sequences). These form primarily the core region- connected by loop regions (for example, β-bends) Super secondary structures are usually produced by packing side chains from adjacent secondary structural elements close to each other . Common AA found at turns are: glycine: small size allows a turn proline: geometry favors a turn

13. Tertiary Structure The configuration of all the atoms in the protein chain: side chains prosthetic groups helical and pleated sheet regions

14. Tertiary Structure Protein folding attractions: 1. Non covalent forces a. Inter and intrachain H bonding b. Hydrophobic interactions c. Electrostatic attractions (+ to - ionic attraction) d. Complex formation with metal ions e. Ion-dipole 2. Covalent disulfide bridges A  protein domain  is a conserved part of a given protein sequence and (tertiary) structure  that can  evolve , function, and exist independently of the rest of the protein chain

15. Tertiary interactions

16. Quaternary Structure Quaternary structure is the result of non covalent interactions between two or more protein chains. Oligomers are multisubunit proteins with all or some identical subunits. The subunits are called protomers. two subunits are called dimers four subunits are called tetramers

17. PROTEIN MISFOLDING Amyloid disease Misfolding of proteins may occur spontaneously, mutation in a particular gene, Abnormal proteolytic cleavage Results in accumulation of insoluble, spontaneously aggregating proteins, called amyloids , implicated in many degenerative diseases—particularly in the age-related neuro-degenerative disorder, Alzheimer disease

18. Prion disease The prion protein (PrP) strongly implicated as the causativeagent of transmissible spongiform encephalopathies (TSEs),including Creutzfeldt-Jakob disease in humans, scrapie in sheep, and bovine spongiform encephalopathy in cattle (popularly called “mad cow disease”).

19. Fibrous vs. Globular Proteins 1. Compact protein structure Extended protein structure 2. Soluble in water (or in lipid Insoluble in water (or in lipid bilayers) bilayers) 3. Secondary structure is complex Secondary structure is simple with a mixture of α -helix, β -sheet based on one type only and loop structures 4. Quaternary structure is held Quaternary structure is usually together by noncovalent forces held together by covalent bridges 5. Functions in all aspects of Functions in structure of the body metabolism (enzymes, transport, or cell (tendons, bones, muscle, immune protection, hormones, etc). ligaments, hair, skin) Globular Fibrous

20. Recommended B Lehninger’s Principles of Biochemistry Lippincott’s Biochemistry

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