The superfamily of leucine-rich repeat proteins can be subdivided into
at least six subfamilies, characterised by different lengths and cons
ensus sequences of the repeats. It was proposed that the repeats from
different subfamilies retain a similar superhelical fold, but differ i
n the three-dimensional structures of individual repeats. The sequence
-structure relationship of three new subfamilies was examined by molec
ular modelling; I provide structural models for the repeats of all sub
families. The models enable me to explain residue conservations within
each subfamily. Furthermore, the difference in the packing explains w
hy the repeats from different subfamilies never occur simultaneously i
n the same protein. Finally, these studies suggest different evolution
ary origins for the different subfamilies. The approach used for the p
rediction of the leucine-rich repeat protein structures can be applied
to other proteins containing internal repeats of about 20 to SO resid
ue in length. (C) 1998 Academic Press Limited.