Human Mpp11 J Protein: Ribosome-Tethered Molecular Chaperones Are Ubiquitous

Abstract

The existence of specialized molecular chaperones that interact directly with ribosomes is well established in microorganisms. Such proteins bind polypeptides exiting the ribosomal tunnel and provide a physical link between translation and protein folding. We report that ribosome-associated molecular chaperones have been maintained throughout eukaryotic evolution, as illustrated by Mpp11, the human ortholog of the yeast ribosome-associated J protein Zuo. When expressed in yeast, Mpp11 partially substituted for Zuo by partnering with the multipurpose Hsp70 Ssa, the homolog of mammalian Hsc70. We propose that in metazoans, ribosome-associated Mpp11 recruits the multifunctional soluble Hsc70 to nascent polypeptide chains as they exit the ribosome.

Hsp110 Cooperates with Different Cytosolic HSP70 Systems in a Pathway for de Novo Folding

“…Instead, Hsp70 binds to polypeptides both co-and post-translationally (4), while probably also interacting with Hsp110 (39). Addi- tional regulatory features are probably also conserved in mammalian cells in light of the recent characterization of the mammalian Zuo1p homologue (47,48). Perhaps the functions of SSB and SSA are encompassed by the mammalian Hsp/Hsc70 homologues, raising the possibility of a handover between ribosome-bound Hsp70 and soluble Hsp70.…”

Why Molecular Chaperones Buffer Mutational Damage: A Case Study With a Yeast Hsp40/70 System

“…Nevertheless, in yeast the cotranslationally acting Ssb's appear functionally distinct from multipurpose Hsp70's, such as Ssa1-4 (Craig et al 2003). This is in contrast to mammalian systems where a multipurpose Hsp70 is also recruited to the cotranslational folding by a ribosometethered Zuo1 homolog (Hundley et al 2005). For these reasons, we selected the Ssb-RAC system as especially attractive for the study of the phenotypic buffering that results from the activity of chaperones during folding of nascent proteins.…”

The flip side of the coin: Role of ZRF1 and histone H2A ubiquitination in transcriptional activation

“…ZRF1 has been studied as a protein attached to ribosomes that is involved in protein-fidelity control, where it functions together with heat shock proteins that bind to its DnaJ domain. 17,18 Our data now suggests that ZRF1 additionally plays a fundamental role during the course of cellular differentiation. We mapped the Ubiquitin-binding domain (UBD) of ZRF1 to a region C-terminal of the DnaJ domain.…”