Regulating ammonia and water transport across membranes; QED!
November 11, Tue 2008
1:00 pm, MRB 100
Dr. Robert Stroud
Professor of Biochemistry & Biophysics, Professor of Pharmaceutical Chemistry, University of California San Francisco
How are small organic molecules filtered and transported into and out of the cell without leaking similar molecules? Transmembrane conduction and signaling depend on integral membrane proteins that serve as transporters, channels, or receptors. Structures of classes of these molecules instruct into their mechanisms of specificity and action. Mechanisms of transport of ammonia, the choice nitrogen source for bacteria, while toxic in mammals, is a highly selective, and highly regulated process. The mechanism transports ammonia without any leakage of ions or even water. This is in spite of the similarity of the dipole moment of NH3 to that of H2O. It also does so without leak of potassium ions with their very similar ionic radius to that of NH4+. The process is regulated by the ‘health’ of the cell. Both the energetic health of the cell, defined by the ATP to ADP ratio, and the carbon health of the cell gate the transport. Both are ‘sensed’ by a PII type transcriptional activator, GlnK that plays key roles in this regulation, acting both in transcription and as a channel blocker. Its function is determined both by covalent modification, by uridylylation, and by non-covalent sensory mechanisms. Molecular structures show how a guanidinium ion mimics ammonium ions in the regulatory process. Glycerol transport by aquaglyceroporins, and water transport by others of the aquaporin family illustrate a different highly selective mechanism that serves to insulate against any leakage of ions, or protons. The structure of a key member of the family that conducts glycerol as efficiently as a glycerol channel, water as effectively as a water channel, and ammonia, instructs in the determinants of selectivity and suggests a new level of electrochemical selectivity. Structure helps to answer why a single mutation serves to transform the channel into a purely glycerol channel with essentially no water conductance. Quod erat demonstrandum or quantum electrodynamics?