2.3.6 Globular Proteins: Structure & Function

Structure

• Globular proteins are
  • Compact
  • Roughly spherical (circular) in shape
• Globular proteins form a spherical shape when folding into their tertiary structure because:
  • Their non-polar hydrophobic R groups are orientated towards the centre of the protein away from the aqueous surroundings
  • Their polar hydrophilic R groups orientate themselves on the outside of the protein
• The folding of the protein due to the interactions between the R groups results in globular proteins having specific shapes
• Some globular proteins are conjugated protein that contain a prosthetic group 

Function

• The orientation of their R groups enables globular proteins to be (generally) soluble in water as the water molecules can surround the polar hydrophilic R groups
• The solubility of globular proteins in water means they play important physiological roles as they can be easily transported around organisms and be involved in metabolic reactions
  • For example, enzymes can catalyse specific reactions and immunoglobulins can respond to specific antigens

Haemoglobin

• Haemoglobin is a globular protein which is an oxygen-carrying pigment found in vast quantities in red blood cells
• It has a quaternary structure as there are four polypeptide chains
  • These chains or subunits are globin proteins (two α–globins and two β–globins) and each subunit has a prosthetic haem group
• The four globin subunits are held together by disulphide bonds
  • Their hydrophobic R groups are facing inwards (helping preserve the three-dimensional spherical shape)
  • Their hydrophilic R groups are facing outwards (helping maintain its solubility)
• The arrangements of the R groups is important to the functioning of haemoglobin
• If changes occur to the sequence of amino acids in the subunits this can result in the properties of haemoglobin changing
  • This is what happens to cause sickle cell anaemia (where base substitution results in the amino acid valine (non-polar) replacing glutamic acid (polar) making haemoglobin less soluble)
• The prosthetic haem group contains an iron II ion (Fe²⁺) which is able to reversibly combine with an oxygen molecule forming oxyhaemoglobin and results in the haemoglobin appearing bright red
• Each haemoglobin with the four haem groups can therefore carry four oxygen molecules (eight oxygen atoms)

The molecular structure of haemoglobin showing the α–globin and β–globin subunits, the prosthetic haem group with oxygen molecules bonded to form oxyhaemoglobin

• Haemoglobin is responsible for binding oxygen in the lungs and transporting the oxygen to tissue to be used in aerobic metabolic pathways
• As oxygen is not very soluble in water and haemoglobin is, oxygen can be carried more efficiently around the body when bound to the haemoglobin
• The presence of the haem group (and Fe²⁺) enables small molecules like oxygen to be bound more easily because as each oxygen molecule binds, it alters the quaternary structure (due to alterations in the tertiary structure) of the protein which causes haemoglobin to have a higher affinity for the subsequent oxygen molecules and they bind more easily
• The existence of the iron II ion (Fe²⁺) in the prosthetic haem group also allows oxygen to reversibly bind as none of the amino acids that make up the polypeptide chains in haemoglobin are well suited to binding with oxygen