Origins of chemoreceptor curvature sorting in Escherichia coli

Abstract

Bacterial chemoreceptors organize into large clusters at the cell poles. Despite a wealth of structural and biochemical information on the system's components, it is not clear how chemoreceptor clusters are reliably targeted to the cell pole. Here, we quantify the curvature-dependent localization of chemoreceptors in live cells by artificially deforming growing cells of Escherichia coli in curved agar microchambers, and find that chemoreceptor cluster localization is highly sensitive to membrane curvature. Through analysis of multiple mutants, we conclude that curvature sensitivity is intrinsic to chemoreceptor trimers-of-dimers, and results from conformational entropy within the trimer-of-dimers geometry. We use the principles of the conformational entropy model to engineer curvature sensitivity into a series of multi-component synthetic protein complexes. When expressed in E. coli, the synthetic complexes form large polar clusters, and a complex with inverted geometry avoids the cell poles. This demonstrates the successful rational design of both polar and anti-polar clustering, and provides a synthetic platform on which to build new systems.

Physical model of protein cluster positioning in growing bacteria

“…Since  c c 2 3 , we can neglect the c 3 term except at very high values of M, which then indicates an exponential decay of the distribution with cluster size (equation (19) is not applicable for arbitrarily large values of M, since our approximations break down). We also see this decay in figure 6, and a similar exponential decay in cluster size distribution is seen experimentally [13,22].…”

“…Moreover, we study the distribution of cluster sizes and dependence of cluster growth on size, since these can be measured experimentally [11,13] and compare the results from our simulations with expressions based on simplified analytical calculations. As was discussed in [22], cluster size distributions also have biological significance in the context of polar localization of chemotaxis receptors. Finally, we study how uniform expansion of the cell (corresponding to spherical growth) would affect such spontaneous cluster positioning.…”

An oscillating MinD protein determines the cellular positioning of the motility machinery in archaea

“…The distribution pattern of chemosensory arrays in H. volcanii superficially resembles that of E. coli, although there are some apparent differences 44 . Several factors are suggested to play a role in the correct spatiotemporal positioning of chemosensory arrays of E. coli, such as: free diffusion and capture of receptors [56][57][58] , a preference for membrane curvature 59,60 , interactions with the Tol-Pal system 61 and others. In E. coli, ParA/MinD seem not important for the positioning of chemosensory arrays 56 .…”

Biophysical and Structural Studies of Escherichia coli Mechanosensitive Channel of Large Conductance in Lipid Bilayers

“…A relationship between membrane protein function and membrane curvature has been documented with other proteins as well (Davies et al, 2012;Draper & Liphardt, 2017;Hahn et al, 2016;Jiko et al, 2015;Pliotas et al, 2015). Some membrane proteins such as chemoreceptors tend to passively cluster on the curved edges of membranes due to the energetic favourability (Draper & Liphardt, 2017) whereas in others such as MscS (Pliotas et al, 2015) and ATP synthases (Daum et al, 2013;Davies et al, 2012;Dudkina et al, 2005;Hahn et al, 2016) the proteins actively induce localised membrane curvature, which can then lead to higher global curvature and clustering in the case of the latter.…”

“…Some membrane proteins such as chemoreceptors tend to passively cluster on the curved edges of membranes due to the energetic favourability (Draper & Liphardt, 2017) whereas in others such as MscS (Pliotas et al, 2015) and ATP synthases (Daum et al, 2013;Davies et al, 2012;Dudkina et al, 2005;Hahn et al, 2016) the proteins actively induce localised membrane curvature, which can then lead to higher global curvature and clustering in the case of the latter. Molecular dynamics simulations have shown MscL capable of inducing local curvature as well , so an interesting area of future study would be to identify if (Nakayama et al, 2015), and 2) liposomes for drug delivery systems need to be smaller than 200 nm to be able to filter through physiological barriers such as blood vessels (Sawant & Torchilin, 2012).…”