  In the cell, proteins fold and perform complex functions through global
structural rearrangements. Function requires a protein to be at the brink of
stability to be susceptible to small environmental fluctuations, yet stable
enough to maintain structural integrity. These apparently conflicting behaviors
are exhibited by systems near a critical point, where distinct phases merge $-$
a concept beyond previous studies indicating proteins have a well-defined
folded/unfolded phase boundary in the pressure-temperature plane. Here, by
modeling the protein phosphoglycerate kinase (PGK) on the temperature (T),
pressure (P), and crowding volume-fraction ($\phi$) phase diagram, we
demonstrate a critical transition where phases merge, and PGK exhibits large
structural fluctuations. Above the critical temperature (Tc), the difference
between the intermediate and unfolded phases disappears. When $\phi$ increases,
the Tc moves to a lower T. We verify the calculations with experiments mapping
the T-P-$\phi$ space, which likewise reveal a critical point at 305 K and 170
MPa that moves to a lower T as $\phi$ increases. Crowding places PGK near a
critical line in its natural parameter space, where large conformational
changes can occur without costly free energy barriers. Specific structures are
proposed for each phase based on simulation.
