The pH affects the stability of protein-protein complexes by altering the ionization states of amino acid side chains, which in turn influences the overall charge, conformation, and interactions between proteins. Protein-protein complexes are stabilized by various types of interactions, including electrostatic, hydrogen bonding, hydrophobic, and van der Waals forces. Changes in pH can disrupt these interactions, leading to changes in protein stability and function.Here is some evidence to support this statement:1. Electrostatic interactions: The ionization states of acidic Asp, Glu and basic Lys, Arg, His amino acid side chains are pH-dependent. At a specific pH, known as the pKa, these side chains can either be protonated charged or deprotonated uncharged . Changes in pH can alter the overall charge of the protein, affecting the electrostatic interactions between proteins. For example, at a pH below the pKa of a basic residue, the side chain will be protonated and positively charged, while at a pH above the pKa, it will be deprotonated and uncharged. This can lead to either the formation or disruption of electrostatic interactions between proteins, affecting complex stability.2. Hydrogen bonding: Changes in pH can also affect hydrogen bonding between proteins. For instance, the ionization state of the side chain of histidine His can influence its ability to form hydrogen bonds. At a pH close to its pKa, histidine can act as both a hydrogen bond donor and acceptor, while at other pH values, its hydrogen bonding capacity may be reduced. This can lead to changes in protein-protein interactions and complex stability.3. Conformational changes: Changes in pH can induce conformational changes in proteins, which can affect their ability to interact with other proteins. For example, the ionization state of amino acid side chains can influence the formation of salt bridges, which are important for maintaining protein structure. Changes in pH can disrupt these salt bridges, leading to conformational changes that affect protein-protein interactions and complex stability.4. Experimental evidence: Numerous studies have demonstrated the effects of pH on protein-protein complex stability. For example, a study by Schreiber and Fersht 1995 showed that the stability of the barnase-barstar complex, a well-characterized protein-protein interaction, is highly dependent on pH. They found that the complex was most stable at pH 6, where the electrostatic interactions between the proteins were optimal. At higher or lower pH values, the stability of the complex decreased due to changes in the ionization states of amino acid side chains and the disruption of electrostatic interactions.In conclusion, the pH affects the stability of protein-protein complexes by influencing the ionization states of amino acid side chains, which in turn affects the overall charge, conformation, and interactions between proteins. Changes in pH can disrupt electrostatic interactions, hydrogen bonding, and salt bridges, leading to changes in protein stability and function. Experimental evidence supports the importance of pH in modulating protein-protein complex stability.