Proteins and their Functions

Structure
R = charged non-polar hydrophobic
 Primary structure – amino
acid sequence – covalent
peptide bonds [N-C]
 Polypeptide structure with
projecting side chains -may
be negatively charged
(Asp/Glu) positively
charged (Arg/Lys), polar
(hydrophilic) or non-polar
(hydrophobic)
 Long polypeptide chains are flexible and this can affect function
 Secondary structure– helices, pleated sheets –non-covalent hydrogen bonds,
electrostatic interactions, van der Waals attraction

 Tertiary structure – three-dimensional

conformation - proteins fold into a tertiary
structure that requires the lowest energy - would
not have negative and negative or hydrophobic
and hydrophilic next to each other
 Quaternary structure –
 a complex of more than
 one polypeptide chain.
 Not rigid structures- conformation is dynamoc and can shift during enzme activation
of substrate binding (induced ift). Phosphorylation is often involved. (HIV Protease)

primary > secondary > tertiary > quaternary

amino acid alpha helix, folded more than

beta sheets
sequence protein one
protein
(peptide bonds)

 Protein structure – X-ray crystallography, nuclear magnetic resonance, Cryo-EM

Functions
 binding (eg ligands and receptors)
 catalysis (eg enzymes)
 switching (eg signalling pathways)
 structural (eg cytoskeletal elements

Regulated Processes of Proteins

 synthesis (is it present or not?)
 localisation (is it where it needs to be?)
 modification (is it active/inactive?)
 degradation (is it needed anymore?)

Regulation of Protein Function

 Regulation of gene expression
 many proteins are only synthesized when and where they are needed
 for example
 during cell differentiation and specialisation
 in the immune response
 In response to signals from other cells

Localisation of Proteins in the cell

 Virtually all proteins are synthesised on ribosome in the cytosol of a cell
 Each protein contains a sorting signal to direct it to the correct site in the cell
 Proteins move from the cytosol into organelles via transporters located in the
membrane
 The secretory pathway transports proteins via transport vesicles.

 Most proteins are modified in the endoplasmic reticulum

 Includes disulphide bonds and
glycosylation (sugars added)
 Further modified in the Golgi apparatus
 Phosphorylation can inhibit or activate
protein and induces a conformational change
( catalysed by protein kinase and dephosphorylation
by phosphatase)
 Growth Factor Signalling

• Membrane receptor activation- leads to

dimerisation and phosphorylation
• Cytoplasmic signalling-
an adaptor protein binds to
phosphorylated receptor
Ras binds to adaptor

Mutations

 By insertions, deletions, substitutions and translocations in DNA

 Changes amino acid sequence
 Mutations acquired or inherited

EXAMPLE: Cystic Fibrosis

• mutated membrane protein (CFTR)
• most common mutation caused by deletion of phenylalanine 508 (DF508)
• mutated protein is incorrectly folded, and retained in endoplasmic reticulum
(degraded, never reaches the membrane)

UPR unfolded protein response

• UPR works as a homeostatic response to keep a cells folding capacity in balance with
its needs.
• An imbalance in this process leads to ER stress and an increase in unfolded proteins.
• Can inhibit translation and lead to cell death

Summary
• Protein sequence determines structure, which determines
function
• Changes in protein structure change protein function
• Location of protein in the cell is important for function
Principle behind normal regulation and cause of pathogenic
change