Thorpe Lab

oxidative protein folding

Augmenter of liver regeneration – an enigmatic flavoprotein

Human augmenter of liver regeneration (ALR, a.k.a. hepatopoietin, HSS, GFER) is the most enigmatic of those sulfhydryl oxidases that show homology with the flavin binding domain of QSOX.  Early studies showed that damaged liver releases a circulatory growth factor eventually found to be a small flavin-linked sulfhydryl oxidase.  ALR is found both extracellularly and intracellularly.  It is particularly abundant in the intermembrane space of the mitochondrion where it drives the retention of certain proteins via disulfide bond insertion:

 

Our work on ALR involves both the short (cytokine-like) and long (mitochondrial) form of the enzyme.  The figure shows the placement of the isoalloxazine ring of the FAD cofactor and the redox active (proximal) disulfide within the core flavin-binding domain.  The longer form (bar diagram) has an additional N-terminal extension that we have found is crucial for interaction with MIA40.

 

alr_homology_lf_small

 

Recently we have worked with the laboratory of Dr. Brian Bahnson to obtain a crystal structure of the short form of human ALR  (PubMed).  

 

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