Biomedical subjects

Bert Poolman

Publications and source records attributed to Bert Poolman.

40 records · Page 3Linked to original sources

PubMed2002

Quaternary structure and function of transport proteins.

Membranes are important sites for the regulation of metabolic functions because they contain transport molecules, which often catalyze the first step in a pathway, and signal-transduction components, which allow the cell to communicate with the environment. Given the catalytic importance of transport proteins and their role in membrane stability, it is possible that oligomerization is used to regulate their function. This review evaluates knowledge of the functions that are associated with the oligomeric organization of secondary transport proteins, which are a major class of solute-translocation systems in all living species.

Animals↗

PubMed2002

How do membrane proteins sense water stress?

Maintenance of cell turgor is a prerequisite for almost any form of life as it provides a mechanical force for the expansion of the cell envelope. As changes in extracellular osmolality will have similar physicochemical effects on cells from all biological kingdoms, the responses to osmotic stress may be alike in all organisms. The primary response of bacteria to osmotic upshifts involves the activation of transporters, to effect the rapid accumulation of osmoprotectants, and sensor kinases, to increase the transport and/or biosynthetic capacity for these solutes. Upon osmotic downshift, the excess of cytoplasmic solutes is released via mechanosensitive channel proteins. A number of breakthroughs in the last one or two years have led to tremendous advances in our understanding of the molecular mechanisms of osmosensing in bacteria. The possible mechanisms of osmosensing, and the actual evidence for a particular mechanism, are presented for well studied, osmoregulated transport systems, sensor kinases and mechanosensitive channel proteins. The emerging picture is that intracellular ionic solutes (or ionic strength) serve as a signal for the activation of the upshift-activated transporters and sensor kinases. For at least one system, there is strong evidence that the signal is transduced to the protein complex via alterations in the protein-lipid interactions rather than direct sensing of ion concentration or ionic strength by the proteins. The osmotic downshift-activated mechanosensitive channels, on the other hand, sense tension in the membrane but other factors such as hydration state of the protein may affect the equilibrium between open and closed states of the proteins.

Bacterial Proteins↗

PubMed2002

ABC transporters: one, two or four extracytoplasmic substrate-binding sites?

Two families of ATP-binding cassette (ABC) transporters in which one or two extracytoplasmic substrate-binding domains are fused to either the N- or C-terminus of the translocator protein have been detected. This suggests that two, or even four, substrate-binding sites may function in the ABC transporter complex. This domain organization in ABC transporters, widely represented among microorganisms, raises new possibilities for how the substrate-binding protein(s) (SBPs) might interact with the translocator. One appealing hypothesis is that multiple substrate-binding sites in proximity to the entry site of the translocation pore enhance the transport capacity. We also discuss the implications of multiple substrate-binding sites in close proximity to the translocator in terms of broadened substrate specificity and possible cooperative interactions between SBPs and the translocator.

ATP-Binding Cassette Transporters↗

PubMed2002

Transporters and their roles in LAB cell physiology.

For most metabolic pathways, the uptake of the substrate into the cell represents the first step. This transport reaction can exert a large control on the flux through the pathway, in particular when the substrate concentration becomes limiting. Besides serving a role in the uptake of nutrients and the excretion of metabolic (end)products or drugs, transport systems can have one or more other functions in the physiology of the cell. Two of these functions, control of carbohydrate utilization and regulation of cell volume, have been well established in lactic acid bacteria (LAB). The first example concerns the phosphoenolpyruvate-dependent phosphotransferase system (PTS), which serves a role in the transport of sugars into the cell but also regulates the activity of metabolic pathways, either through regulation of transcription and/or (in)activation of transporters and key enzymes already present. The regulation by the PTS results in a hierarchy in the utilization of sugars and/or adjustment of the first step(s) of a metabolic pathway to the metabolic capacity of the cell and the availability of a particular substrate. The second example relates to the activation of transporters (and mechanosensitive channels), which represents the first mechanism of defence against osmotic stress. The activation by osmotic-upshift of the ATP-binding Cassette (ABC) transporter OpuA from Lactococcus lactis is compared with the activation by osmotic-downshift of mechanosensitive channels. The mechanosensitive channels have been best studied in organisms other than LAB, but the presence of similar systems in LAB, and their conservation of structure, suggest that the postulated functions and mechanisms generally hold.

Bacterial Proteins↗