3D Structure Of Proteins Flashcards
Folding of polypeptide chain is determined by:
Amino acid sequence Molecular structure + properties of its amino acids Molecular environment (solvents + salts)
Amino acids fall into categories defined by …… and …… properties
Structural
Chemical
Properties of amino acids are determined by their structure
Properties of individual amino acids are determined by variable side chain
Charged amino acids may be subdivided into acidic(-ve) and basic (+ve)
Charged amino acids are polar in nature
Carboxyl groups COO- are …… or ….
Charged or acidic
Amine groups NH3^+ are ……. or……..
Charged or basic
2^o amine groups NH + carbonyl group C=O are …….
Polar
Hydroxyl group OH^- are …….
Polar
Hydrocarbon is. ……..
Non-polar hydrophobic
Describe the structure of peptide bond?
Is flat planar structure with rotational freedom within molecule found around alpha carbon
What role does non covalent bonding play in determining folding?
Weak
Determine most of structure
What role of electrostatic attraction in determining folding?
Falls off exponentially as distance increases, affected by electrostatic environment
Typically occurs in aqueous environment
What are Van Der Waals attraction?
Weak forces occur between 2 atoms in non covalent attractions
Determined by their fluctuating change
Attraction at close distance is balanced by repulsion due to proximity that is determined by VDW radius of an atom
VDW forces are induced by proximity of molecules
What are hydrophobic interactions?
H2O is polar molecule
Hydrophobic interactions minimise disruption of H2O network
4th weak force
What are forces determining protein structure?
Electrostatic interaction= attraction of oppositely charged groups such as carboxyl and amine groups of aspartic acid and lysine
Hydrogen bonds
Hydrophobic effect
VDW interaction
What are disulphide bonds?
Covalent bonds
Form between side chains of 2 cysteine molecules
Bonds form in oxidative reaction
SH group from each cysteine cross link
Can form on same (intra-chain) or different (inter-chain) polypeptide chains
What is primary structure?
Covalent bonds forming polypeptide chain
Order of amino acid residues joined by peptide bonds
What is secondary structure?
Regular folded forms stabilised H bonds
What is tertiary structure?
Overall 3D structure stabilised by H bonds, hydrophobic, ionic + VDW’s forces + sometimes by intra-chain covalent (disulphide) bonds
What is quaternary structure?
Organisation of polypeptide into assemblies, stabilised by non-covalent + covalent bonds + sometimes by inter-chain covalent (disulphide) bonds
Give examples of secondary structure
Beta sheets
Beta turns
Alpha helices
How are alpha helices formed?
Formed from intra-chain H bonding
Usually H bond between every 4th residue
How are beta sheets formed?
Formed from intra-chain H bonding which is formed between adjacent beta strands to stabilise the sheets
How are beta sheets arranged?
Can have 2 different arrangements where strands are either parallel or anti-parallel
How are beta turns arranged?
Very specific arrangement of peptide chain forming U-shaped structure stabilised by H bonds
Beta often contain glycine or proline
Tertiary structure involves combining…
Secondary structures of single polypeptide
Quaternary structure involves combining …..
Multiple chains
Which constitutes functional molecule
What happens to function of mis-folded protein?
Is almost always lost +reduced
What do misfolded proteins often have tendency to do?
Have tendency to self associate + form aggregates
E.g. Huntington’s, Alzheimer’s, Parkinson’s disease, type 2 diabetes etc
Other misfolded proteins result in cellular processing that lead to their degradation e.g. cystic fibrosis
What are the reasons why misfolding occurs?
Somatic mutations in gene sequence
Errors in transcription or translation
Failure of folding machinery
Mistakes of post-translational modifications or in trafficking of proteins
Structural modifications produced by environmental changes
Induction protein mis folding by seeding and cross seeding by other proteins
