Three Times Two Is Six

See allHide authors and affiliations

Science  09 Nov 2007:
Vol. 318, Issue 5852, pp. 888
DOI: 10.1126/science.318.5852.888a

Photosynthetic organisms take advantage of an abundance of nitrogen by storing it as arginine (whose side chain contains a nitrogen-rich guanidinium group), a reaction that is catalyzed by the dimeric protein N-acetylglutamate kinase (NAGK)—an enzyme that is, not surprisingly, subject to feedback inhibition by arginine. PII proteins are one of the central metabolic coordinators of carbon and nitrogen fluxes; this protein is a homotrimer and has been shown previously to regulate ammonia influx into cells by inserting its T loop into the cytoplasmic vestibule of the trimeric ammonia channel; too much of a good thing can be hazardous to one's acid/base equilibrium.

Llácer et al. describe structural and biochemical studies of the interaction between PII and NAGK in the cyanobacterium Synechococcus. They show that a hexameric ring (a trimer of dimers) of NAGK is sandwiched by a pair of PII trimers, so that each of the six PII subunits makes a reversible contact covering about 600 Å2 with a single NAGK subunit. Each NAGK dimer is oriented at an angle to the plane of the ring, as in the blades of a propeller, and the binding of PII increases the angle slightly. The arginine-binding sites are located at the interdimer surfaces, and tilting the dimers and altering the interdimer contacts reduces the binding affinity for arginine by 15-fold. Unlike its direct inhibition of the ammonia channel, the effect of PII binding on NAGK, though also mediated in large part by the T loop, is entirely indirect and distant from both the catalytic and allosteric sites.— GJC

Proc. Natl. Acad. Sci. U.S.A. 104, 17644 (2007).

Navigate This Article