Assembly of PGAM5 into Multimeric Complexes Provides a Mechanism for Allosteric Regulation of Phosphatase Activity

Methods in Enzymology
Peter A TiptonMark Hannink

Abstract

Phosphoglycerate mutase family member 5 (PGAM5) is a serine/threonine phosphatase that has been localized to both inner and outer mitochondrial membranes. PGAM5 has been suggested to regulate multiple aspects of mitochondrial dynamics, including fission/fusion and mitophagy, through phosphatase-dependent and phosphatase-independent mechanisms. Understanding how the phosphatase activity of PGAM5 is regulated will provide new insight into signaling mechanisms that link changes in cell physiology with mitochondrial function. In this chapter, we describe methods for obtaining both multimeric and dimeric complexes of PGAM5 and for characterizing their kinetic properties. The ability to purify different PGAM5 complexes and to characterize their kinetic properties will enable detailed biophysical studies of the quaternary structures of the various PGAM5-containing complexes. The phosphatase activity of different PGAM5 complexes varies over three orders of magnitude. We suggest that the ability to generate PGAM5 complexes that have a wide range of phosphatase activities will facilitate screens to identify small molecules that modulate the phosphatase activity of PGAM5.

Citations

Aug 14, 2021·Acta Pharmaceutica Sinica. B·Chenglong GaoTao Pang

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