Scaffolding proteins are proteins that are required to catalyse, regulate o
r modulate some step in the assembly of a macromolecular complex. They asso
ciate specifically with the nascent protein complex during assembly, but ar
e subsequently removed, and are absent from the mature structure. Scaffoldi
ng proteins have been described primarily from viral systems, in particular
from the double-stranded DNA bacteriophages, but most likely play a more g
eneral role in macromolecular assembly, a fundamental process in all biolog
ical systems. Scaffolding proteins may act in a specific fashion, by active
ly encouraging the formation of correct protein-protein interactions, or mo
re generally by nucleating and promoting assembly. They may also work to en
sure the fidelity of the assembly process by preventing the formation of im
proper interactions, in many ways similar to the role of molecular chaperon
es in protein folding. In viruses, scaffolding proteins are found both in t
he form of internal cores and external. bracing, and may form elaborate and
complex structures. This review will focus on the viral scaffolding protei
ns, for which an increasing amount of structural and functional information
has recently become available.