MCBG Session 5 - Protein Structure Flashcards
Outline the structure of amino acids.
- Each amino acid (except for proline) has a carboxyl group, a primary amino group, and a distinctive side chain (“R-group”) bonded to the α-carbon atom.
- In proteins, almost all of these carboxyl and amino groups are combined through peptide linkage and, in general, are not available for chemical reaction except for hydrogen bond formation
- Thus, it is the nature of the side chains that ultimately dictates the role an amino acid plays in a protein.
- It is, therefore, useful to classify the amino acids according to the properties of their side chains, that is, whether they are nonpolar (have an even distribution of electrons) or polar (have an uneven distribution of electrons, such as acids and bases).
Outline the structure and function of amino acids with non-polar side chains.
- Each of these amino acids has a nonpolar side chain that does not gain or lose protons or participate in hydrogen or ionic bonds.
- The side chains of these amino acids can be thought of as “oily” or lipid-like, a property that promotes hydrophobic interactions.
- In proteins found in aqueous solutions––a polar environment––the side chains of the nonpolar amino acids tend to cluster together in the interior of the protein.
- However, for proteins that are located in a hydrophobic environment, such as a membrane, the nonpolar R-groups are found on the outside surface of the protein, interacting with the lipid environment.
Identify the non-polar amino acids.
- Glycine
- Alanine
- Valine
- Leucine
- Isoleucine
- Phenylaline
- Tryptophan
- Methionine
- Proline
Outline the structure and function of amino acids with uncharged polar side chains.
- These amino acids have zero net charge at neutral pH, although the side chains of cysteine and tyrosine can lose a proton at an alkaline pH.
- Serine, threonine, and tyrosine each contain apolar hydroxyl group that can participate in hydrogen bond formation.
- The side chains of asparagine and glutamine each contain a carbonyl group and an amide group, both of which can also participate in hydrogen bonds.
Identify uncharged polar side chains.
- Serine
- Threonine
- Tyrosine
- Asparagine
- Glutamine
- Cysteine
Outline the structure and formation of a disulphide bond.
- Disulphide bond: The side chain of cysteine contains a sulfhydryl group (–SH), which is an important component of the active site of many enzymes.
- 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–).
- Many extracellular proteins are stabilized by disulphide bonds. E.g. Albumin, a blood protein that functions as a transporter for a variety of molecules.
Outline the structure and function of amino acids with acidic side chains.
- The amino acids 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-).
- They are, therefore, called aspartate or glutamate to emphasize that these amino acids are negatively charged at physiologic pH.
Outline the structure and function of amino acids with basic side chains.
- The side chains of the basic amino acids accept protons.
- At physiological pH the side chains of lysine and arginine are fully ionized and positively charged.
- In contrast, histidine is weakly basic, and the free amino acid is largely uncharged at physiological pH.
- However, when histidine is incorporated into a protein, its side chain can be either positively charged or neutral, depending on the ionic environment provided by the polypeptide chains of the protein.
- This is an important property of histidine that contributes to the role it plays in the functioning of proteins such as haemoglobin.
Outline the acidic and basic properties of amino acids.
- Amino acids in aqueous solution contain weakly acidic α-carboxyl groups and weakly basic α-amino groups.
- In addition, each of the acidic and basic amino acids contains an ionisable group in its side chain.
- Thus, both free amino acids and some amino acids combined in peptide linkages can act as buffers.
- Acids may be defined as proton donors and bases as proton acceptors.
- Acids (or bases) described as “weak” ionize to only a limited extent.
- The concentration of protons in aqueous solution is expressed as pH where or –log [H+].
- The quantitative relationship between the pH of the solution and concentration of a weak acid (HA) and its conjugate base (A–) is described by the Henderson-Hasselbalch equation.
Outline the derivation of the equation.
Outline the structure of proteins.
- Primary structure
- Secondary structure
- Tertiary structure
- Quarternary structure
What are the biochemical roles of proteins?
- Catalysts – enzymes
- Transporters (e.g. O2, Fe)
- Structural support (e.g. collagens in skin and bone)
- Machines – (e.g. muscular contraction and motion)
- Immune protection (e.g. immunoglobulins)
- Ion channels
- Receptors (e.g. for hormones, neurotransmitters, etc.)
- Ligands in cell signalling (e.g. growth factors etc.)
Outline the key features of proteins.
- Proteins are polypeptides – macromolecules composed of amino acids. Amino acids join covalently to form the sequence of the protein.
- The amino acid sequence of a protein determines: the way the polypeptide chain folds and the physical characteristics of the protein.
- The polypeptide chain folds into a complex and highly specific 3D structure, determined by the sequence of the amino acids.
- The folding of proteins depends on the chemical and physical properties of the amino acids.
- The amino acid sequence of a protein is encoded by a gene. The nucleotide sequence of a gene determines the amino acid sequence of a protein.
Discuss the ionisation states of amino acids.
Discuss how amino acids can be classified based on their chemical and physical properties.
- Chemical properties
I. Hydrophobic
II. Hydrophilic
III. Polar
IV. Non-polar
V. Acidic
VI. Basic
VII. Neutral
- Physical properties
I. Aliphatic
II. 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.
Discuss the pK values of ionisable side chains.
Discuss the charge of amino acids at physiological pH (7.4)
Outline the structure and formation of peptide bonds.
- Peptide bond formation: the linking of two amino acids is accompanied by the abstraction of a molecule of water (condensation reaction/dehydration synthesis).
- Peptide bonds are planar: Ca, C, O, N and H all lie in the same plane
- Peptide bonds are rigid: The peptide bond C-N has partial double bond characteristics (resonance hybrid) and hence unable to rotate – contributes to planarity
- Peptide bonds exhibit a trans conformation
- Bonds on either side of the peptide bond are free to rotate.
Outline 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.
- 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.
- If the pH < pI then the protein is protonated.
- If the pH > pI then the protein is deprotonated.
Discuss the sizes of peptides and proteins.
Biologically active peptides and proteins come in a varying range of sizes:
I. Peptides/ oligopeptides - A few amino acids in length
II. Polypeptides/proteins - Many amino acids
What are conjugated proteins?
Conjugated proteins: some proteins covalently linked chemical components in addition to amino acids
Characterise the different components of protein structure.
- Primary structure: the linear amino acid sequence of the polypetide chain
- Secondary structure: local spatial arrangement of polypeptide backbone - the conformations like helices.
- Tertiary structure: the overall 3D configuration of the protein
- Quaternary structure: association between different polypeptides to form a multi-subunit protein
Compare and contrast globular and fibrous proteins.
Identify the types of tertiary structures found in globular proteins.
- Motifs – folding patterns containing 1/more elements of secondary structure
- Domains – part of a polypeptide chain that fold into a distinct shape. Often has a specific functional role
Outline the quaternary structure of proteins.
- Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins.
- However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated.
- The arrangement of these polypeptide subunits is called the quaternary structure of the protein.
- Subunits are held together by noncovalent interactions (E.g. hydrogen bonds, ionic bonds, and hydrophobic interactions).
- Subunits may either function independently of each other, or may work cooperatively, as in haemoglobin, in which the binding of oxygen to one subunit of the tetramer increases the affinity of the other subunits for oxygen.
