Replacement of glycine 227 in the fifth WD40 motif of ${alpha}$-COP/Ret1p/Soo1p by charged or aromatic amino acids is responsible for the temperature-dependent osmo-sensitivity of Saccharomyces cerevisiae, while truncations of WD40 motifs exerted a reduction in cell growth rate and impairment in assembly of cell-wall associated proteins such as enolase and Gas1p. Yeast two-hybrid analysis revealed that the ret1-1/soo1-1 mutation of ${alpha}$-COP abolished the interaction with ${eta}$- and ${varepsilon}$-COP, respectively, and that the interaction between ${alpha}$-COP and ${eta}$-COP relied on the WD40 domain of ${alpha}$-COP. Furthermore, although the WD40 domain is dispensable for interaction of ${alpha}$-COP with ${varepsilon}$-COP, structural alterations in the WD40 domain could impair the interaction.