quaternary protein structure

Meaning: Quaternary structure is the arrangement of multiple folded polypeptide subunits in a complex. The subunits can be identical (homodimer) or different (heterodimer). The same kinds of interactions that stabilize tertiary structure hold the subunits together: hydrophobic interactions, hydrogen bonds, and ionic interactions, with disulfide bonds between chains in some proteins. Hemoglobin is the standard example, with four subunits (two α and two β). Binding of O₂ to one subunit shifts the conformation of the others, so binding is cooperative and the O₂ binding curve is sigmoidal.

On the MCAT: Expect passages on hemoglobin cooperativity or allosteric enzymes, where a change at one subunit alters the others. Gel questions are also common. SDS-PAGE disrupts noncovalent interactions, so subunits separate and run by mass. Adding a reducing agent such as β-mercaptoethanol also breaks disulfide bonds between chains. Native PAGE keeps the complex intact. You may be asked to predict how a mutation at a subunit interface, or a denaturing agent, affects function.

Common confusion: Students call any large protein with several domains or disulfide bonds quaternary. Quaternary structure requires more than one separate polypeptide chain. One chain folded into several domains, or with disulfide bonds inside it, is still tertiary structure.