Peptides and Protein Architecture

• There are 20 types of amino acids that can form dipeptides and tripeptides.
• Each residue has two rotatable backbone bonds, allowing for different conformations but for a given amino acid sequence, only one typically forms.

Peptides

• Small peptides have specific uses; Aspartame is metabolised into Aspartic acid, Phenylalanine and methanol.
• Phenylketonuria patients cannot ingest Phenylalanine and as such should not have Aspartame.
• Glutathione is a tripeptide with anti-oxidant properties.

Noncovalent Interactions

• Noncovalent interactions are weak but they stabilise protein structure.

• Electrostatic attractions occur due to the presence of positive and negative charges.

• Hydrogen bonds form between a hydrogen atom and an electronegative atom.

• Van der Waals attractions are weak and depend on transient dipoles.

• a folded peptide chain, which defines the overall conformation.

• The quaternary structure describes the interaction oProtein Architecture

  • Proteins aren't just simple chains of amino acids. They feature four levels of structure
  • The primary structure is the order of amino acids in the chain
  • The secondary structure consists of repeating patterns related to hydrogen bonds
  • The tertiary structure is the 3D structure of f multiple subunits in proteins.

Primary Protein Structure

• The primary structure is the sequence of amino acids covalently bonded together.
• Peptide bonds form the backbone of proteins
• Side chains do not participate in peptide bond formation.

Secondary Protein Structure

• The secondary structures of a protein describe the foldings that occur due to hydrogen bonds
• α-helix structures describe a helical structure of the amino acid residues.
• Carbonyl oxygen atoms form hydrogen bonds to amide hydrogen atoms four residues away in alpha-helices.
• Not every AA forms α-helices, the order of AA & their separation is important too

ẞ-pleated sheets

• ẞ-sheets occur when strands are laterally packed together.
• Side chains are either antiparallel or parallel to one another.

Tertiary Protein Structure

• Tertiary structures are the folding and bonding of the amino acid sequence to form a three dimensional structure.
• The final folded form of many proteins interfold between beta sheets and alpha helices.
• These structures can be globular (spherical) or extended rods.

Protein Folding

• Protein folding driven by hydrophobic forces in the cells aqueous environment
• Hydrophobic R-groups are found on the inside of the protein
• Hydrophilic R-groups are found on the outside.
• This increases the protein's stability, leading to folded confirmations in an aqueous environment.

Quaternary Protein Structure

• The quaternary structure exists in proteins with multiple subunits, describing arrangements/contacts of those subunits.
• Haemoglobin is a protein with 4 subunits composed of 2 alpha and 2 beta subunits.
• Molecular complementarity: stable complexes can occur between the protein subunits.

Protein Domains

• Chains of over 200+ AA often fold into compact stable structures known as domains.
• Domains feature a specific function, such as binding of small molecules
• Many domains are structurally independent, with features like small proteins.

Transmembrane Proteins

• Transmembrane proteins have alpha-helical regions that allow them to embed in phospholipid bilayers
• Hydrophobic regions of the alpha helix interact with the lipids.

Rigid Cores

• Some proteins consist of Rigid cores of ẞ-Sheets

Protein Sequences

• Knowing the AA sequence of a protein is useful.
• Comparison of 'normal' & 'variant' proteins are used to compare proteins from different species for evolution
• Determining the 3D structure of a protein is important.
• The order of amino acids (primary structure) determines its function, but changes can have no effect, a little effect, or an enormous effect on the 3D structure.

Insulin

• Insulin is a protein hormone with two chains: alpha and beta, with 51 amino acids.
• First protein primary structure to be determined in 1953
• Made in the pancreas and is secreted when blood glucose levels rise, which causes the liver to uptake glucose.

Insulin and Diabetes

• Diabetics require insulin that is sourced from different species.
• Can have: cow (3 AA different), pig (1 AA different), sheep (4 AA different) or human insulin.
• This is due to the similar tertiary and quaternary structures which allows the insulins to function. However, human insulin works most efficiently.

Disulphide Bonds

• Di-sulphide bonds stabilise protein conformation.
• These bonds are covalent
• Can be interchain or intrachain

Haemoglobin

• Haemoglobin transports oxygen, and is comprised of 4 subunits consisting of alpha and beta subunits.
• Pathological condition has a single AA change in the beta chain, resulting in sickle cell anaemia.
• Inherited disease effects ~ 4/1000 in some populations
• People can before age 30 due to Infection, kidney failure, heart failure and thrombosis
• Caused from a glutamic acid - polar that changes to to a valine - nonpolar
• Disrupts folding into the correct 3-D shape, meaning the protein cannot work properly.
• A single AA substitution results in a severely defective protein.

Protein Classification

• Shape of a chain consisting of amino acids is vital in determining function either for a simple protein (AA only) or a conjugated protein
• Many proteins contain only AA and nothing else and are simple proteins, like insulin.
• Some proteins contain other chemical components in addition to amino acids, and are known as conjugated proetins like hemogloblin.
• The non-amino acid part of conjugated proteins is known as a prosthetic group.
• Lipoproteins contain lipids
• Metalloproteins contain a specific metal
• Glycoproteins contain sugar groups (Glykos = sweet) and are commonly found in proteoglycans

Metals and Proteins

• Metals in cells have diverse roles, and can be found as ions that are either bound to biomolecules or free in solution
• Metals can form covalent links by receiving electrons from a nonmetal donor, which creates a coordinate bond
• These are either between nitrogen, oxygen, and or sulfur
• Iron forms coordinate bonds with Nitrogen in Hb
• Isopeptide bonds form between the side chain amino group of Lys & another amino acid
• Ubiquitinylation occurs when target proteins undergo degradation
• Transglutaminaton forms crosslinks between proteins in insoluble polymers in blood clots