Molecules, genes and cells - PROTEINS

Zwitterion

a molecule or ion having separate positively and negatively charged groups. - amino acids

Domain

Different secondary structures together

Peptide bond

Double bond characteristics = stiff = cannot rotate.

CORN clockwise

L isomer (found in nature)

CORN anticlockwise

D isomer

Histone proteins

DNA packaging. Many Arg and Lys = basic residues with pos charge = attraction to neg DNA.

Sickle cell anaemia mutation

Glu to Val in Hb.

HbS form stiff needles and destroy RBC.

Cystic Fibrosis mutation

Deletion of Phe in CFTR

Trans or Cis peptide bond orientation in polypeptides

Usually trans due to the steric constraints of cis - R clashes.

What is the exception?

Proline as clashes either way

Amide plane

C-CO-NH-C

Phi

the torsion angle of NH-C

Psi

the torsion angle of C-CO

Non-covalent bonds in proteins

Hydrogen, Salt bridges, Van der Waals

Hydrogen bonds

Needed for protein folding. Main chain atoms. NH-CO

Salt bridges

Electostatic attractions between amino acids.

+ Arg, Lys

- Glu, Asp

Van der Waals

Weak attractions between molecules or parts of molecules that result from transient local partial charges - fluctuating dipoles.

secondary structures

alpha helices, beta strands--> sheets, hairpins/loops

RH alpha helices

clockwise

beta sheets

Hydrogen binds between NH-CO on different but adjacent beta strands. Parallel or antiparallel strands. R above or below sheet.

Hydrophobic effect in protein folding

Decreased entropy of the protein folding, increase entropy of the surrounding water molecules.

Tertiary structures - 3D

alpha-helical domains, beta-sandwich, beta-barrel, alpha/beta

Alpha-helical domains

Coiled coils or bundles

Eg, Lac Repressor

Beta-sandwich

2 beta-sheets with hydrophobic filling

Beta-barrel

8 betas strands in a closed barrel, hydrophobic centre (aqueous environment)

alpha/beta structures

1) barrel - alpha outside

2) open-linked beta sheet - Rossman fold

Chaperones

help proteins fold correctly

Cofactors

Perform specific chemical reactions within enzyme active sites, oft vitamins.

Prosthetic groups

Non-protein groups in a protein complex, such as heme in Hb

Immunoglobulins, Ig

Y shaped globular proteins made from B cells that recognise epitopes.

Epitopes

Antigens

Antibody-antigen complexes can trigger...

Complement cascade which punches holes in membranes - membrane attack sequence - Tc & perforin.

Why are hinge regions important?

For epitopes that are differing distances apart.

How are Ig's stabilised?

Same as protein folding - the non-covalent bonds.

Heavy chains of Ig

4 domains - 3 constant, 1 variable

Light chains of Ig

2 domains - 1 constant, 1 variable

Hypervariable regions

small regions of high amino acid sequence diversity within the variable regions of immunoglobulin

How many HVRs per Ig?

6

3 light, 3 heavy

Constant regions

beta-sandwich

4 : 3 = 7 strands total

Variable regions

beta-sandwich

4 : 5 = 9 strands total

Where are the HVRs located in the variable regions?

The loops between beta strands - HVR1,2,3 per face.