In the ribonuclease superfamily, dimericity is a unique feature of bov
ine seminal RNase (BS-RNase). In about two-thirds of native BS-RNase m
olecules, the two subunits interchange their N-terminal tails, thus ge
nerating domain-swapped dimers (MxM), which mostly responsible for enz
yme biological activities and allostericity. Higher molecular weight B
S-RNase oligomers can also be prepared [Libonati, M. (1969) Ital. J. B
iochem. 18, 407-417.]. This paper reports on BS-RNase tetrameric deriv
atives which were isolated and enzymatically characterized. The data c
ollected and the analysis of the crystal packing of MxM dimers suggest
ed a structural model for tetramer assembly, in which the four subunit
s are enchained by multiple domain-swapping events.