Definitions

Cooperative binding

• Describes unique interactions between heme groups in hemoglobin
• Small movement of heme group propagates through hemoglobin’s 3D structure

HEMOGLOBIN STRUCTURE

R-form (relaxed)

• Alpha-alpha interactions: weak ionic and H-bonds form salt bridges
• Beta-beta interactions: no interactions; move apart upon oxygenation
• Alpha-beta dimers: strong hydrophobic interactions within each dimer

T-form (tense)

• 3D structure changes between oxygenated and deoxygenated states

HEME SITE

T-form (tense)

• Heme site: when O2 leaves, iron center moves out of porphyrin plane & proximal histidine moves away from iron center
• Small movement in heme group makes O2 binding unfavorable

SALT BRIDGES

• Salt bridges break and reform upon oxygen binding –> peptide wiggle-room
• Alpha chain salt bridges:
  – Alpha1: arginine carboxy terminus (-) and arginine side group (+)
  – Alpha2: lysine (+) and aspartate (-)
• Salt bridges regulate cooperativity: iron centers move into porphyrin planes

DISSOCIATION CURVE

• % oxygen saturation vs. oxygen partial pressure (torr)
• Cooperative binding produces sigmoidal binding curve
• After hemoglobin reaches 50% saturation: saturation increases rapidly (steepest point of curve)
• Hemoglobin O2 affinity rapidly increases at half saturation