On 2013 Nov 12, Lillian Kenner commented:

In a quest to biochemically characterize the Zuo1 protein’s dual role of regulating transcriptional activation and folding of nascent polypeptides via its association with the ribosome, the functional role of the conformational heterogeneity of this protein is explored. Zuo1, a co-chaperone of Hsp70, consists of an RNA-binding domain and an autoinhibited 4 helix bundle located at the C-terminal domain (CTD). Here the authors show that upon unfolding of the CTD of Zuo1, Zuo1 dissociation from the ribosome and subsequently activating of the transcription factor Pdr1.

This paper highlights the multiple functional states sampled by Zuo1, by the novel concept that regulation can be achieved by an equilibrium of protein folding and unfolding. It also establishes that there is a feedback mechanism initiated from Zuo1’s primary role in translation to regulate transcriptional activity. The authors state that though they are among the first to establish signalling through an unfolding mechanism, they are not the first group to find a link between ribosomal associated proteins and transcriptional regulators.

There are still plenty of questions that could be followed up on. What would cause the unfolding necessary for activation of Prd1? And by what mechanism does this unfolding lead to dissociation from the ribosome? Though this is briefly addressed in the paper by saying that based on thermal unfolding measurements they calculate the CTD to be unfolded 4% of the time, or that perhaps that unfolding is caused by another binding partner.

On 2013 Nov 12, Lillian Kenner commented:

In a quest to biochemically characterize the Zuo1 protein’s dual role of regulating transcriptional activation and folding of nascent polypeptides via its association with the ribosome, the functional role of the conformational heterogeneity of this protein is explored. Zuo1, a co-chaperone of Hsp70, consists of an RNA-binding domain and an autoinhibited 4 helix bundle located at the C-terminal domain (CTD). Here the authors show that upon unfolding of the CTD of Zuo1, Zuo1 dissociation from the ribosome and subsequently activating of the transcription factor Pdr1.

This paper highlights the multiple functional states sampled by Zuo1, by the novel concept that regulation can be achieved by an equilibrium of protein folding and unfolding. It also establishes that there is a feedback mechanism initiated from Zuo1’s primary role in translation to regulate transcriptional activity. The authors state that though they are among the first to establish signalling through an unfolding mechanism, they are not the first group to find a link between ribosomal associated proteins and transcriptional regulators.

There are still plenty of questions that could be followed up on. What would cause the unfolding necessary for activation of Prd1? And by what mechanism does this unfolding lead to dissociation from the ribosome? Though this is briefly addressed in the paper by saying that based on thermal unfolding measurements they calculate the CTD to be unfolded 4% of the time, or that perhaps that unfolding is caused by another binding partner.