GEK1532 Proteins

Thorsten Wohland Dep. Of Chemistry S8-03-06 Tel.: 6516 1248 E-mail: chmwt@nus.edu.sg

Book: Biochemistry, Voet, chapter 4 and chapter 7 http://www.cellsalive.com/

Critique of the WCS

Are there non-trivial constraints on colour categorization? B.A.C. Saunders, J. van Brakel Behavourial and Brain Sciences (1997), 20, 167-179 1. Color is an objective property equally defined by all human beings. 2. Hue, Saturation and Brightness completely describe color. 3. There are 4 hues: green, red, blue, yellow 4. The unique hues are defined by so- called opponent channels. That is, the brain always compares a) red (L come) to green (M cone) and b) blue (S cone) to yellow (M cone + L cone).

Problem
We have reviewed different theories that can explain different aspects of our color vision: 1. Tristimulus theory: Since we can mix all colors with 3 (abstract colors) our vision should be based on three different sensors (cones). The theory can explain complementary colors, metamers and is a good tool for the classification of colors. 2. Opponent color theory: This theory is based on 4 colors (plus an achromatic brightness channel). It explains many effects of perception not easily explained by the tristimulus theory: hue cancellation experiments, existence of only two different kinds of dichtomacy (red-green, blue-yellow deficiencies). Then we took a look at the WCS and its criticism by Saunders and Brakel. This showed that few of the things we took for granted up to now are really evident or have a unshakable basis. So is there any basis on which we can found our investigation of color vision?

Hydrophobic effect
In the liquid phase most water molecules are hydrogen bonded

O H + H H

O H + H

O H + H O + H

O H + H O H + H

O H + H H

O + H H O

O H + H

Hydrophobic effect
We get a separation of the non-polar molecule from water; We say the molecule is hydrophobic (it hates water).

O H + H H

O H + H

O H + H O + H

O H + H

O H + H

Introducing non-polar, hydrophobic elements like the tail of a lipid into water disrupts the structure of water

Revision: Forces + + + -

O H + H

O H + H

Hydrogen bonding

Electrostatic forces Van der Waals forces, dipole interactions

O H+ H O H+ H O H+ H
Hydrophobic effect

- + +-

+ + -

O H+ H O H+ H

+-

London dispersion forces

Revision: Hydrophilicity, Hydrophobicity, and Amphipathicity

H2O Hydrophilic: water loving, dissolves well in water + Alcohol (ethanol) H2O Hydrophobic: water hating, dissolves badly in water + oil H2O Amphipathic: consist of a hydrophilic and a hydrophobic part + lipid

Revision: What are lipids?

Glycerophospholipids Polar head group

backbone

Non-polar, hydrophobic tail

Revision: Amphipathic molecules

Hydrophobic Hydrophilic

Revision: Why membranes?

Compartmentalization: The bilayer separates the inside of a cell (the cytoplasm or intracellular space) from the outside of the cell (extracellular space) Na+, Cl2-5 nm

Average residence time of water molecules: 0.02 s Average residence time of ions (Cl- or Na+): 8 h

Proteins
Proteins are the molecules that are at the center of activity in biological processes. Enzyme: they catalyze reactions. Regulators: they regulate all kinds of action in the cell or body. Storage and transport: E.g. O2 transport in blood. Signal transduction: they hand on signals and are responsible form communication. Sensors: eyes, taste, smells All proteins are built out of 20 basic building blocks, so called amino acids. These amino acids have different properties and the sequence in which they are put together to build a protein determines how the protein functions and what it does. The sequence of the amino acids in the proteins is given in the DNA.

Amino Acids

C R NH2 H COOH L-amino acid D-amino acid

Peptide bond
In aqueous solution (pH=7.4)

A possible sequence

You have the choice of 20 amino acids at every position in a protein/peptide. Thus for a di-peptide you have 20*20 = 400 possibilities. For a tri-peptide you have 20*20*20 = 8000 possibilities. For a peptide with 10 aa you have 2010 = 10240*109 possibilities. Proteins have anything between 30 to 1000 aa!

Interactions
1. Polar amino acids with polar parts of lipids (heads) or aqueous solutions 2. Nonpolar amino acids with nonpolar parts of lipids (lipid tails)

Interactions
3. Hydrogen bonds (polar amino acids with polar amino acids)

Hydrogen bonding

See e.g.: http://www-structure.llnl.gov/Xray/tutorial/protein_structure.htm

Structure elements

Secondary Structure
E-helix F-sheet

Tertiary Structure
Secondary structure elements

3D structure, side view

3D structure, top view

Tertiary Structure

Quartenary Structure

If several single polypeptide strands assemble together to form a protein we speak of a quartenary structure of the protein. Of course every strand in this protein has its own primary, secondary and tertiary structure.

Protein function
Proteins in the cell have several functions: 1. Structural functions => cytoskeleton Cell shape, cell movement, intracellular transport

http://www.biology.arizona.edu/cell_bio/ tutorials/cytoskeleton/page1.html

2. Enzymatic functions Increase of reaction rates at physiological conditions (pH=7.4, 37 C) with high specificity and the possibility of regulation by control of enzyme numbers. 3. Signal transduction, transport of molecules

Signal transduction, transport of molecules

Receptor proteins
Receptors are proteins on the cell surface that can recognize signals in form of molecules from the outside: neurotransmitters, hormones.

Yes

Lock and key mechanism No The receptor now changes its conformation on the inside and other proteins can bind to the receptor.

Ligand 1. Receptor Outside of cell (extraxellular space)

Protein inside the cell

Inside of cell (cytoplasm)

2. Binding of ligand to receptor

3. Conformational change and binding of other proteins on the inside

Receptors: ligand-gated channels

Ions can flow (Ca2+, Na+, K+ etc.)

Receptors: Inhibition

Ions cannot flow (Ca2+, Na+, K+ etc.)

Receptor proteins
Transmission of signals from outside to inside of a cell
Binding of ligands outside Conformational changes
A) Binding of proteins on the cytoplasmic side B) Opening of a pore for ion transport

Inhibition

Energy source
Many of the reactions catalyzed need some energy to proceed. This energy is often provided by so-called triphosphates The triphosphates can be converted into di- or monophosphates to release energy that is stored in their molecular bonds. There exist not only ATP but as well the other triphosphates GTP, UTP, CTP. ATP -> ADP -> AMP ATP: Adenosine triphosphate ADP: Adenosine diphosphate AMP: Adenosine monophosphate

Summary
There are 20 amino acids with varying characteristics (polar, non-polar, charged) The secondary and higher structure of proteins is determined by the sequence of amino acids (primary structure) and their interactions with each other The correctly folded protein can have several functions: structural, enzymatic, communication and transport The most important proteins for us are the so-called receptor proteins that establish the communication between cells or of cells with the outside. Vision, olfaction and taste are all based on receptor proteins that recognize specific signals