SCID 141 - LIVING PROCESS: FROM MOLECULES TO CELLINSTRUCTOR: KITTISAK YOKTHONGWATTANA, PH.D.

DEPARTMENT OF BIOCHEMISTRY, FACULTY OF SCIENCE, MAHIDOL UNIVERSITY

AMINO ACIDS AND PROTEINS

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AMINO ACIDS

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STEREO CHEMISTRY OF AMINO ACIDS

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DIFFERENT SIDE CHAINS OF AMINO ACIDS

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DIFFERENT SIDE CHAINS OF AMINO ACIDS

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DIFFERENT SIDE CHAINS OF AMINO ACIDS

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DIFFERENT SIDE CHAINS OF AMINO ACIDS

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DIFFERENT SIDE CHAINS OF AMINO ACIDS

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AMINO ACID ABBREVIATION

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AMINO ACID ABBREVIATION

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COVALENT BOND FORMATION BETWEEN AMINO ACIDS – DISULFIDE BOND

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PROTONATION STATES OF AMINO ACIDS

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PROTONATION STATES OF AMINO ACIDS

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PEPTIDE BOND FORMATION

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POLYPEPTIDE CHAIN – PRIMARY STRUCTURE

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POLYPEPTIDE CHAIN FOLDS INTO SECONDARY STRUCTURE

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AND ANGLES

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RAMACHANDRAN PLOT

Image from Voet and Voet, Biochemistry, 4th Edition, 2011

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WHAT DO AND ANGLES SIGNIFY?

Image from Voet and Voet, Biochemistry, 4th Edition, 2011

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POLYPEPTIDE CHAIN FOLDS INTO SECONDARY STRUCTURE – ALPHA HELIX

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MOLECULAR INTERACTION STABILIZING SECONDARY STRUCTURE IS HYDROGEN BOND

Image from Lippincott, Fig. 2.6

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POLYPEPTIDE CHAIN FOLDS INTO SECONDARY STRUCTURE – ALPHA HELIX

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POLYPEPTIDE CHAIN FOLDS INTO SECONDARY STRUCTURE – BETA SHEET

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POLYPEPTIDE CHAIN FOLDS INTO SECONDARY STRUCTURE – BETA SHEET

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SECONDARY STRUCTURES FOLD INTO TERTIARY STRUCTURE

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INTERMOLECULAR INTERACTIONS THAT STABILIZE TERTIARY STRUCTURE

Disulfide bond formation

Hydrophobic interactionImages from Lippincott, Fig. 2.9, 2.10

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INTERMOLECULAR INTERACTIONS THAT STABILIZE TERTIARY STRUCTURE

Ionic interaction

Images from Lippincott, Fig. 2.11

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SOLUBLE PROTEIN

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CHAPERONE-ASSISTED PROTEIN FOLDING – DnaK/DnaJ SYSTEM

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CHAPERONE-ASSISTED PROTEIN FOLDING – GroEL/GroES SYSTEM

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TRANSMEMBRANE PROTEIN

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TRANSMEMBRANE PROTEIN

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TRANSMEMBRANE PROTEIN

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TRANSMEMBRANE PROTEIN

Aquaporin

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VOLTAGE-GATED K+ CHANNEL

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EXAMPLE OF CHLORIDE CHANNEL

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QUATERNARY STRUCTURE OF PROTEIN IS THE ASSEMBLY OF TERTIARY STRUCTURES

http://upload.wikimedia.org/wikipedia/commons/3/3d/1GZX_Haemoglobin.png

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DISULFIDE BOND FORMATION ALSO STABILIZES PROTEIN QUATERNARY STRUCTURE

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PROTEIN FOLDING SIGNIFIES FUNCTIONS

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COLLAGEN IS A TRIPLE-HELIX PROTEIN

The stability of collagen triple helices rely on a sharp turn of the helix caused by an amino acid called hydroxyproline. Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl hydroxylase following its de novo synthesis (as a post-translational modification). Such reaction, which requires vitamin C, takes place in the lumen of the endoplasmic reticulum.

http://en.wikipedia.org/wiki/Hydroxyproline#mediaviewer/File:Hydroxyproline_structure.svg

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ACTIN – MYOSIN ARE MAJOR PROTEINS IN MYOCYTES

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ACTIN – MYOSIN ARE MAJOR PROTEINS IN MYOCYTES

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ACTIN – MYOSIN ARE MAJOR PROTEINS IN MYOCYTES

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MYOSIN MOTOR

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ACTIN

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MOVEMENT OF MYOSIN MOTOR ON ACTIN FILAMENT

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IMMUNOGLOBULIN PROTEINS - IgG

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IMMUNOGLOBULIN PROTEINS

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IMMUNOGLOBULIN PROTEINS - IgM

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PHAGOCYTOSIS OF AN ANTIBODY-BOUND VIRUS BY A MACROPHAGE

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HEMOGLOBIN

MyoglobinHemoglobin

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HEME STRUCTURE WITHIN HEMOGLOBIN UPON OXYGEN BINDING

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THE BOHR EFFECT

CO2 and H+ ions also are effectors of hemoglobin. In active muscle cells, oxygen is rapidly consumed and carbon dioxide and H+ ions are produced.O2 affinity decreases at lower pH. As hemoglobin moves into a tissue with lower pH, it can more easily unload oxygen.

Increase in CO2 concentrations have the same effect.

In combination, the effect of pH and CO2 allow nearly 90% of the oxygen bound in the lungs to be unloaded in tissues where it is required.

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STRUCTURAL BASIS OF THE BOHR EFFECT

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BPG BINDING STABILIZES THE T STATE

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SICKLE CELL ANEMIA