Poly-Glu, or polyglutamic acid, forms an α-helical structure in aqueous solution at low pH due to protonation of its side chains, which minimizes electrostatic repulsion and stabilizes the helix. The correct answer is (A) 3.​

Option Analysis

At pH 3, glutamate side chains (-COOH) are protonated and neutral, allowing hydrogen bonding in the backbone to form a stable α-helix without charge repulsion.​
At pH 7, side chains deprotonate to -COO⁻ (pKa ~4.3), introducing negative charges that cause repulsion and favor random coil over helix.​
At pH 9 or 12, full deprotonation intensifies repulsion, completely destabilizing the helix in favor of extended coil.​

Poly-Glu, or poly-L-glutamic acid (PGA), undergoes a reversible helix-coil transition controlled by solution pH, making it a classic model for studying protein secondary structure in biochemistry and CSIR NET life sciences. This pH dependence arises from the ionizable carboxylic acid side chains (pKa ≈ 4.3) of glutamate residues.​

Helix Formation Mechanism

The α-helical structure relies on intramolecular hydrogen bonds between backbone carbonyls and amide hydrogens every 3.6 residues. In poly-Glu α-helical structure pH below 5 (especially pH 3), side chains protonate to neutral -COOH, eliminating repulsion and enabling tight helix packing. Circular dichroism (CD) spectra confirm high helix content (0.3–0.6) in acidic conditions.​

Coil Transition at Neutral/High pH

Above pH 5, deprotonation yields -COO⁻ charges spaced ~1.5 nm apart in the helix, causing electrostatic repulsion that unwinds the structure into random coil. This is evident in MD simulations and osmotic pressure studies, where higher pH requires extreme pressures (>100 MPa at pH 7) to induce helix. Unfolding starts at the C-terminus, propagating via turn/3₁₀-helix intermediates.​