A broad view of scaffolding suggests that scaffolding proteins can actively control regulation and signaling of multienzyme complexes through allostery

► We classify multienzyme complexes based on the presence of scaffolding proteins. ► Scaffolding proteins typically allosterically regulate signaling multienzyme complexes. ► Scaffolding proteins are rare in metabolic multienzyme complexes. ► Allostery plays a key role in the presence and absence of scaffolding proteins. ► Scaffolding proteins can control pathway branching in multienzyme complexes.