An amino acid sequence motif, called the WD. 40 repeat, has b~en found as a repeat in a large variety of proteins that do not share any obvious functional properties. At present, the function of the repeated motif is not known for any of these proteins. Interestingly. recent experiments in yeast indicate that several proteins containing the WD-40 repeat are genetically associated with members of the TPR-family. a protein family that is characterized by the presence of another repeated motif of unknown function: the tetratrieopeptide repeat, it is conceivable that proteins containing the WD--t0 repeat interact physically with ~aenabers of the TPg-family via their respective repeated motifs.WD-40 repeat; G protein B-subunit; Protein family; TPR-gene familyMany proteins contain repeated motifs that may be considered as building blocks, representing structural elements or functional domains. The deduced amino acid sequence of the fl-subunit of heterotrimeric G-proteins revealed that, except for the first 50 N-terminal amino acids, the fl-subunit is comprised of 7 segments that show sequence similarity to each other and are arranged in tandem [1]. This repeated motif, referred to as the WD-40 repeat [2], is characterized by the presence of a number of amino acids, conserved not only with respect to the type of side chain, but also in their spacing. A similar motif has been found in several other proteins. Based on the presence of the WD-40 repeat, these proteins may constitute a WD-40 family.Members of the WD-40 family include: (i) the fl-subunit of guanine nucleotide regulatory proteins (G-proteins), a component of the heterotrimeric complex that transduces signals from transmembrane receptors to a variety of second messenger generating effectors [1,2]; (ii) STE4, a functional G-protein fl-subunit homologue in yeast (Saccharomyces cerevisiae), involved in a signal pathway that controls the response to mating pheromone [3]; (iii) CDC4, a component of the yeast nuclear cytoskeleton, required at the late Gj/S phase boundary of the cell cycle [4,5]; (iv) CDC20, a yeast gene product required for several microtubule-dependent processes at multiple stages in the cell cycle [6][7][8] [24,25]. It should be noted, however, that the second motif in ligninase displays a rather weak homology to the WD-40 consensus sequence. An alignment of all WD-40 repeats identified and a WD-40 consensus sequence based on this alignment are shown in Fig 1. The WD-40 repeat can be divided in 2 relatively conserved elements, A and B, spaced by regions variable in both sequence and length (Fig. I A)