3 Protein domains
That proteins contain functionally and physically discrete modules or domains is an important principle, one that will be reinforced as we examine the roles of specific proteins in a variety of different cellular processes.
There are several advantages conferred by multidomain protein architecture:
Creation of catalytic or substrate-binding sites These sites are often formed at the interface between two domains, typically a cleft. Movement of the domains relative to each other allows the substrate to bind and excludes the solvent to create the environment necessary for catalysis.
Segregation of function Different domains of a protein often have distinct functions. Figure 26 shows a single subunit of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase. The subunit consists of two domains, one that binds the substrate (glyceraldehyde 3-phosphate) and one that binds the NAD coenzyme. Segregation of function in this way permits the swapping of function by swapping of domains. Thus numerous NAD-dependent dehydrogenases share similar domains for binding of NAD, whilst having distinct substrate-binding domains.
Multifunctional proteins A multidomain protein may have more than one function, often related, and each function is performed by a distinct domain. For example, E. coli DNA polymerase I has both polymerase activity, and two kinds of exonuclease activity, all of which are required for DNA replication and all of which reside on distinct domains of this protein.
Why might it be advantageous to have two enzyme activities on the same protein?
Where two activities are required at the same time and in the same place, as in the case of the polymerase and exonuclease activities in DNA polymerase I, it is advantageous to have them on the same protein. The cellular process in which they are involved (DNA replication in this case) will be more efficient as all the necessary activities are ‘on hand’ and are present in equivalent quantities.
Broadly speaking, domains have a structural, catalytic or binding/regulatory function. Catalytic function in proteins will be discussed in detail later in this course.