The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex.

Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in all kingdoms of life. In addition, fungi possess a specialized Hsp70 system attached to ribosomes, which in Saccharomyces cerevisiae consists of the Hsp70 homologs Ssb1/2p, Ssz1p, and the Hsp40 homolog zuotin. Ssz1p and zuotin are assembled into a unique heterodimeric complex termed ribosome-associated complex. So far, no such specialized chaperones have been identified on ribosomes of higher eukaryotes. However, a family of proteins characterized by an N-terminal zuotin-homology domain fused to a C-terminal two-repeat Myb domain is present in animals and plants. Members of this family, like human MPP11 and mouse MIDA1, have been implicated in the regulation of cell growth. Specific targets of MPP11/MIDA1, however, have remained elusive. Here, we report that MPP11 is localized to the cytosol and associates with ribosomes. Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related homolog of Ssz1p. Complementation experiments indicate that mammalian ribosome-associated complex is functional in yeast. We conclude that despite a low degree of homology on the amino acid level cooperation of ribosome-associated chaperones with the translational apparatus is well conserved in eukaryotic cells.