Q$4\mathrm{.}3-$Explain in molecular terms how binding of O$2$ to Fe$2+$ in hemoglobin causes a protein conformational change resulting in a $1$ tilt in the F helix. Be specific.

Describe three conditions that explain why hemoglobin is fully saturated with O$2$ in the lungs and how these same three conditions differ in tissues resulting in O$2$ dissociation from hemoglobin.