Hemoglobin quaternary transition: what initiates the T → R conformational change? Identify the event that first triggers the switch from the low-affinity T state to the high-affinity R state.

Introduction / Context:
Hemoglobin exhibits positive cooperativity, switching from the T to the R state as oxygen binds. Dissecting the sequence of structural events clarifies how small ligand-induced changes propagate into large quaternary rearrangements.

Given Data / Assumptions:

• Each subunit contains a heme with Fe2+ coordinated to a proximal histidine.
• Allosteric transition involves local and global structural changes.

Concept / Approach:
The initiating event is oxygen binding to ferrous iron in the heme. This pulls Fe2+ into the porphyrin plane, dragging the proximal histidine, shifting the F-helix, and altering inter-subunit contacts. These steps cumulatively convert the tetramer toward the high-affinity R state.

Step-by-Step Solution:
O2 binds to Fe2+ in the heme pocket.Iron moves into the porphyrin plane, pulling the proximal His (F8).The F-helix repositions, causing tertiary changes within the subunit.Quaternary contacts rearrange, stabilizing the R state across the tetramer.

Verification / Alternative check:
X-ray and spectroscopic studies show the iron movement upon O2 binding precedes the larger quaternary shift, confirming the sequence.

Why Other Options Are Wrong:
Proximal His and F-helix movements and subunit contact reorganization are consequences of initial O2 binding, not the initiating step; proton release is part of the Bohr effect, not the trigger.

Common Pitfalls:
Assuming global quaternary change precedes the local heme event. The ligand–heme interaction comes first.

Final Answer:
Binding of oxygen to the heme.