Unit 1 - Protein Synthesis, Structure and Function

Clinical connections

Effects of misfolding, ie disease

Specificity and Flexibility of proteins causes

Risks

Functional Protein

Contributes to cell outcomes in usual conditions with tolerable fail rate

Shape and Structure specificies

Function of the protein

N Terminus

Amino End

C Terminus

Carboxyl end, new ones add to this end

Amino Acids

R groups + H + Amino Groups + COOH

Hydrophobic Amino Acids tend to be in

The core of soluable proteins

Aromatic Amino Acids

• Phenylalanine

• Tyrosine

• Trytophen

Aliphatic Amino Acids

Hydrocarbon chains

• Alanine

• Valine

• Isoleucine

• Leucine

• Methionine

Basic Amino Acids are

Positively charged

• Lysine

• Arginine

Acidic Amino Acids are

Negatively charged

• Aspartic

• Glutamic Acid

Hydrophilic Aminos

• Serine

• Theonine (neutral at 7pH)

• Asparagine

• Glutamine (polar amine)

Cysteine

Disulphide bridges with other cysteine

Glycine

Very small to sqeeze into small spaces and proteins to bend

Proline

R group covalently bonds with amino group creating kink for structure

Histidine

Has amino diethyl that changes positive or negative depending on pH

Peptide bonds forms by

Condensation reaction between amino and COOH

Translation

1. Ribosome subunits assemble to read mRNA

2. tRNA enters A site

3. tRNA shifts to P site, amino chain shifts

4. Used tRNA shifts to E site to be ejected

Primary Structure

1. DNA to mRNA

2. Introns removed from mRNA

3. Exits to cytosol

Random Coil Structure

Periodically ordered structure of protein

Statistical Coil

Protein spends most of its time in a certain structure

Native Structure

Functional protein structure

Hydrophobic Effect

Clumping of nonpolar, noncovalent molecules to aqueous solution to decrease interactions with water that add up for strong stability of folded structure

Setae Fibres in a Geckos Foot

Induces LD dipoles to let geckos walk sideways

Secondarry Structure

Periodic folding of polypeptide into distinct, conserved, geo arrangements

Motifs

Combinations of 2nd structure

Alpha Helixes

Spiral, rod like structure by COO bonds with H 4 positions away, 3.6 aminos per churn

Beta Sheets

Planar structure with 2+ strands aligned by H bonds

Beta Pleated Sheets

Laterally packed beta stranger from H bonds between COOH and amino from backbone in adjacent beta strand

Intramolecular H Bonds

Beta sheet in the polypeptide

Intermolecular H Bonds

Beta sheet betwen polypeptides

Turns/Loops

Connectors of beta and alpha

Beta Turn

3-4 aminos connecting beta strands of sheet

Coiled-Coil Motif

2 alpha helixes wrap aorund each other because both r groups are amphipathic and hydrophobic face inwards when aminos are at position 1 and 4 in repeat of 7 aminos

Zinc Finger Motif

Alpha helixes and 2 beta strands form 2 positioned residues with zinc atom

Beta Barrel Motif

Barrel form when last beta strands forms H-bonds with first strand

Helix Loop Helix Motif

2 alpha helixes joined by a loop region by non covalent interactions between aminos and calcium ion

Tertiary Structure

3D arrangement of all aminos

Domain

Functional unit of protein associated with a unique function and fold independently

Functional Domain

Region with specific activity of protein

Structural Domain

Region with a recognizable shape

Sre protein regulates

Cell cycle

Sre Protein Structure

• Small and large functional kinase domains

• SH2, SH3 structural domains

Quaternary Structure

Number and organization of subunits in a multiple protein complex

Multimeric Protein

Functional protein with multiple polypeptides

Dimer

2 polypeptides or subunits

Trimer

3 polypeptides

Homodimer

2 same polypeptides

Heterodimer

2 different polypeptides

Instrinsically Unstructured Proteins

Proteins that lack teritary structure when alone

Post translation changes

Individual aminos r groups

Lysine + Acetyl

Acetyl Lysine, to protect proteins from proteases

Methylated Histidine Residues

3 methyl histidine

Phosphorylation

PO4 from ATP to OH group of serine, tyrosine, threonine by kinases

Phosphatases

Remove PO4

Proline can be

Hydroxylated, 3 of them create functional collagen

Carboxylation adds

Negative charge

Glycosylation

Add carbohydrates, protect proteins and helps folding

Sugar add to

OH groups of serine and threonine

Lipidation

Anchors proteins to hydrophobic biomembranes

Protein folding is

Spontaneous, reversible, and unique

Reversible Denaturation Experiment

1. Denatured protein with urea to break H bonds, and beta mercaptoethanol to break disulfide bridges

2. Dialysis to remove denaturants which brought it back to original shape

Villin

36 residue, alpha helical protein with hydrophobis core of 3 phenylalanines

Sickle Cell Anemia

Misfolded haemoglobin, tetramer with 2 alpha and beta subunits with two stable native structure

SIckle Cell Mutation

Glutamate to valine at position 6 causes it hydrophobic instead charged and instead of form polymers which gets stuck in capillaries