In the study of protein structure, function and mechanism, transmembrane and membrane proteins (MPs) are of particular interest. MPs constitute 25% of all known proteins and are involved in a host of fundamental biological processes including ion transport and signal transduction across the membrane. Moreover, MPs are targeted by more than 60% of existing drugs. However, in contrast to water-soluble proteins, they are much less well understood. The primary reason for this is their amphiphilic character which leads to complications with their isolation from the membrane and subsequent purification. Indeed, for the study of MPs, one needs to extract them from their native lipid environments into more tractable membrane-mimicking systems. Such difficulties, together with the importance of MPs, make the corresponding research an exciting but challenging problem.Two-component signaling systems (TCS) enable microorganisms to communicate with the environment, are present in all domains of life and are the most abundant signaling systems in Nature. TCS consist of a signal receptor/transducer and a response regulator. The former are usually transmembrane receptors (histidine kinases, chemoreceptors, photoreceptors) which have a similar, modular structure. Most TCS receptors/transducers function as higher order oligomers (trimers of dimers in the case of chemoreceptors). Moreover, the oligomeric state adopted is often dependent on external conditions, which makes structural study of such receptors a difficult task, particularly for full-length systems. The first part of the work described here focuses on structural studies of the full-length NpSRII/NpHtrII receptor/transducer TCS. Crystallization of the full-length system resulted in either very small, poorly diffracting crystals or samples in which the transducer region has undergone proteolysis. Solution scattering (SAXS/SANS) studies described here confirm that the oligomerization and folding of full-length NpSRII/NpHtrII strongly depends on ionic strength of its surrounding solution: at low salt concentration (150 mM NaCl) the complex forms dimers when solubilized in detergent; in high salt buffers (4.0 M NaCl), corresponding to native conditions, these dimers associate to form trimers of dimers. The SAXS/SANS experiments carried out also confirm that full-length NpSRII/NpHtrII is highly conformationally dynamic, a fact which might explain the failure, despite promising initial conditions, for the electron microscopy analysis reported here to produce anything but a very low resolution reconstruction of NpSRII/NpHtrII.While functional dependence of MPs on their surrounding lipids has been well established experimentally, the mechanisms by which lipids modulate MP structure and function are still poorly understood. To shed light on these, the second part of this thesis work examines, using inert gases as models, how small hydrophobic moieties interact with MPs at the molecular level. High pressure techniques were used to produce argon and krypton derivatives of crystals of three well studied MPs (two different proton pumps and a light-driven sodium ion pump). The crystal structures obtained show that a vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of the MPs – a surface buried in the membrane and which usually accommodates the hydrophobic chains of annular lipids. Supplementary analysis by in silico molecular dynamics (MD) carried out here shows an even greater number of potential argon and krypton interaction sites on MP surface within the lipid bilayer. These results suggest that MPs are stabilised in an optimal functional conformation by the specific binding of lipids that energetically best fit the grooves on their hydrophobic surfaces. A concept of a general mechanism of allosteric regulation of MP function by lipids and its alteration by other hydrophobic molecules is thus proposed.