S4-5) Protein Structure Flashcards
Describe the molecular structure of an amino acid
Each amino acid (except for proline) has the following bonded to the α-carbon atom:
- A carboxyl group
- A primary amino group
- A distinctive side chain (“R-group”)
How are amino acids be classified?
- Amino acids are classified according to the properties of their side chains
- The nature of the side chains dictates the role an amino acid plays in a protein
How do amino acids bond together?
Peptide bonds are formed to link two amino acids together accompanied by the abstraction of a molecule of water (condensation reaction/dehydration synthesis)
Describe the 4 unique features of peptide bonds
- Peptide bonds are planar
- Peptide bonds are rigid
- Peptide bonds exhibit a trans conformation
- Bonds on either side of the peptide bond are free to rotate
How might amino acids be classified?
- Polar: uneven distribution of electrons
- Nonpolar: even distribution of electrons
Describe the structure and formation of a disulphide bond
- The side chain of cysteine contains a sulfhydryl group (–SH)
- In proteins, the –SH groups of two cysteines can become oxidized to form a dimer, cystine, which contains a covalent cross-link called a disulphide bond (–S–S–)
What is the significance of disulphide bonds?
- Important component in the active site of many enzymes
- Many extracellular proteins are stabilized by disulphide bonds e.g. Albumin
How can one characterise basic and acidic amino acids respectively?
- Acidic amino acids: negatively charged at physiological pH
- Basic amino acids: positively charged at physiological pH
What is the value of physiological pH?
pH = 7.35 - 7.45
Identify the 2 amino acids with acidic side chains
- Aspartate
- Glutamate
Outline the behaviour of amino acids with acidic side chains
- The aspartic and glutamic acid are proton donors
- At physiological pH, the side chains of these amino acids are fully ionized, containing a negatively charged carboxylate group (–COO-)
Outline the behaviour of amino acids with basic side chains
- The side chains of the basic amino acids accept protons
- At physiological pH the side chains of strongly basic amino acids are fully ionized and positively charged
- At physiological pH, the side chains of weakly basic amino acids the free amino acid is largely uncharged
Identify the 3 amino acids with basic side chains
- Arginine (strongly basic)
- Lysine (strongly basic)
- Histidine (weakly basic)
What is the Henderson-Hasselbalch equation?
What is the significance of the Henderson-Hasselbalch equation?
The Henderson-Hasselbalch equation expresses the quantitative relationship between the pH of a solution and the [weak acid] and the [conjugate base]
What encodes for the amino acid sequence of a protein?
The nucleotide sequence of a gene determines the amino acid sequence of a protein
What is determined by the amino acid sequence of a protein?
- The way the polypeptide chain folds
- The physical characteristics of the protein
Proteins are polypeptides.
What are polypeptides?
- Polypeptides are macromolecules composed of amino acids
- Amino acids join covalently through peptide bonds to form the sequence of the protein
Identify two contrasting factors which influences the way in which a protein folds?
- Chemical properties of the amino acids
- Physical properties of the amino acids
How can amino acids be classified based on their chemical properties?
- Hydrophobic / Hydrophilic
- Polar / Non-polar
- Acidic / Basic / Neutral
How can amino acids be classified based on their physical properties?
Aliphatic / Aromatic
What are amino acid residues?
Amino acid residues are what remains of an amino acid after it has been joined by a peptide bond to form a protein
How do pKa values vary across acidic and basic amino acids?
- Basic amino acids:
I. Positively charged R groups
II. Higher pKa values (6.0 - 12.5)
- Acidic amino acids:
I. Negatively charged R groups
II. Lower pKa values (2.8 - 4.3)
Illustrate the relationship between pK values and pH in terms of amino acids
- pH of the solution < pK value of amino acid = R group is protonated
- pH of the solution > pK value of amino acid = R group is deprotonated
What is meant by the isoelectric point of proteins?
Isoelectric point (pI) of proteins: the pI of a protein is the pH at which there is no overall net charge
How do pI values vary across acidic and basic proteins?
- Basic proteins have a pI > 7 and contain many positively charged (basic) amino acids
- Acidic proteins have a pI < 7 and contain many negatively charged (acidic) amino acids
Illustrate the relationship between pI values and pH in terms of proteins
- If the pH < pI then the protein is protonated
- If the pH > pI then the protein is deprotonated
What are conjugated proteins?
Conjugated proteins are proteins which have other chemical components covalently linked in addition to amino acids e.g. haemoglobin
Identify 5 biochemical roles of proteins
- Catalysts e.g. enzymes
- Transporters e.g. haemoglobin carries O2
- Structural support e.g. collagens in skin and bone
- Immune protection e.g. immunoglobulins
- Receptors e.g. for hormones, neurotransmitters, etc
Identify the 4 different components to protein structure
Describe the primary structure of the protein
Primary structure is the linear amino acid sequence of the polypetide chain
Describe the secondary structure of the protein
Secondary structure is the local spatial arrangement of polypeptide backbone consisting of alpha helixes and beta pleated sheets
Which type of bond stabilises the secondary structure of a protein?
H2 bonds
Describe the tertiary structure of the protein
Tertiary structure is the overall 3D configuration of the protein
Describe the quaternary structure of the protein
Quaternary structure is the association between different polypeptides to form a multi-subunit protein
Identify the 4 interactions which stabilise the tertiary structure
- Disulphide bonds
- Hydrophobic interactions
- Hydrogen bonds
- Ionic interactions
Which bonds hold subunits together in the quaternary structure of the protein?
Non-covalent interactions:
- Hydrogen bonds
- Ionic bonds
- Hydrophobic interactions
How do subunits function in the quaternary structure of proteins?
- Subunits can function independently
- Subunits can function cooperatively e.g. haemoglobin
Describe the role and structure of fibrous proteins and include an example
- Role: support, shape, protection
- Structure: single type of repeating secondary structure, forms long strands or sheets
- Examples: collagen & keratin
Describe the role and structure of globular proteins and include an example
- Role: catalysis, regulation, transport
- Structure: several types of secondary structure
- Examples: myoglobin, haemoglobin, carbonic anhydrase
Identify the 2 types of secondary structures found in globular proteins
- Motifs
- Domains
Describe the 2 types of secondary structures found in globular proteins
- Motifs which are folding patterns containing 1/more elements of secondary structure
- Domains which are the parts of a polypeptide chain that fold into a distinctive shape
How do membrane proteins fold?
Membrane proteins fold to express hydrophobic amino acids on the exterior cell surface and hydrophilic amino acids on the interior forming channels
How do water soluble proteins fold?
In water soluble proteins, polypeptide chains fold so the hydrophobic side chains are buried and polar and the charged side chains are on the cell surface
Describe the relative amount of amino acids in the following:
- Peptides/oligopeptides
- Polypeptides/proteins
- Peptides/oligopeptides: few amino acids in length
- Polypeptides/proteins: many amino acids in length
