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The role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices.

Haselwandter CA, Wingreen NS - PLoS Comput. Biol. (2014)

Bottom Line: In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers.Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties.Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers.

View Article: PubMed Central - PubMed

Affiliation: Departments of Physics & Astronomy and Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

ABSTRACT
In vivo fluorescence microscopy and electron cryo-tomography have revealed that chemoreceptors self-assemble into extended honeycomb lattices of chemoreceptor trimers with a well-defined relative orientation of trimers. The signaling response of the observed chemoreceptor lattices is remarkable for its extreme sensitivity, which relies crucially on cooperative interactions among chemoreceptor trimers. In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers. Here we introduce a biophysical model of bilayer-chemoreceptor interactions, which allows us to quantify the role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices. We find that, even in the absence of direct protein-protein interactions, membrane-mediated interactions can yield assembly of chemoreceptor lattices at very dilute trimer concentrations. The model correctly predicts the observed honeycomb architecture of chemoreceptor lattices as well as the observed relative orientation of chemoreceptor trimers, suggests a series of "gateway" states for chemoreceptor lattice assembly, and provides a simple mechanism for the localization of large chemoreceptor lattices to the cell poles. Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties. Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers.

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Gateway to assembly of face-on trimer configuration.Calculated elastic interaction energy between two chemoreceptor trimers as a function of trimer orientation (upper axes) and center-to-center trimer distance (lower axes), and (A) membrane thickness and (B) membrane tension. Trimer configurations are rotated from the tip-on to the face-on configuration while maintaining reflection symmetry and a minimum edge-to-edge separation of  nm, which yields the face-on trimer configuration at  nm (and the tip-on trimer configuration at  nm). The vertical lines at  nm indicate the face-on trimer separation measured for chemoreceptor lattices [19], [22]. For ease of comparison, the zero energy for each curve was set at the tip-on configuration. For (A) we set  and for (B) we used the monolayer thickness  nm corresponding to the E. coli cytoplasmic membrane. All trimer interaction energies were calculated as in Fig. 2.
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pcbi-1003932-g003: Gateway to assembly of face-on trimer configuration.Calculated elastic interaction energy between two chemoreceptor trimers as a function of trimer orientation (upper axes) and center-to-center trimer distance (lower axes), and (A) membrane thickness and (B) membrane tension. Trimer configurations are rotated from the tip-on to the face-on configuration while maintaining reflection symmetry and a minimum edge-to-edge separation of nm, which yields the face-on trimer configuration at nm (and the tip-on trimer configuration at nm). The vertical lines at nm indicate the face-on trimer separation measured for chemoreceptor lattices [19], [22]. For ease of comparison, the zero energy for each curve was set at the tip-on configuration. For (A) we set and for (B) we used the monolayer thickness nm corresponding to the E. coli cytoplasmic membrane. All trimer interaction energies were calculated as in Fig. 2.

Mentions: Fig. 2 implies a scenario for the assembly of chemoreceptor lattices in which the tip-on trimer configuration is a gateway state yielding attraction between chemoreceptor trimers over several nanometers, with the directionality of membrane-mediated interactions ensuring that, at small separations, trimers are arranged in the face-on orientation allowing further stabilization through direct protein interactions mediated by CheA and CheW [19], [20]. In particular, the interaction potentials in Fig. 2 suggest that the face-on trimer configuration found in chemoreceptor lattices [19], [20] could be achieved through the sequence of gateway states shown in Fig. 3. For large , the tip-on configuration is strongly favored (for ease of visualization, the tip-on configuration is set as the zero of in Fig. 3). As the trimer separation shrinks below the steric constraint on the tip-on configuration, the membrane deformation energy can be lowered further by a symmetric rotation of the chemoreceptor trimers (S1 Video), ultimately yielding the observed face-on trimer configuration [19], [20] as the lowest-energy configuration, thus ensuring correct assembly of chemoreceptor lattices. Consistent with the results in Fig. 2, we find that the membrane-mediated interactions stabilizing the sequence of gateway states in Fig. 3 vanish for lipid bilayers matching the chemoreceptor hydrophobic thickness and increase with the magnitude of the hydrophobic mismatch (Fig. 3A). Similarly, our model predicts that the reduction in membrane deformation energy associated with the sequence of gateway states in Fig. 3 increases with increasing membrane tension (Fig. 3B).


The role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices.

Haselwandter CA, Wingreen NS - PLoS Comput. Biol. (2014)

Gateway to assembly of face-on trimer configuration.Calculated elastic interaction energy between two chemoreceptor trimers as a function of trimer orientation (upper axes) and center-to-center trimer distance (lower axes), and (A) membrane thickness and (B) membrane tension. Trimer configurations are rotated from the tip-on to the face-on configuration while maintaining reflection symmetry and a minimum edge-to-edge separation of  nm, which yields the face-on trimer configuration at  nm (and the tip-on trimer configuration at  nm). The vertical lines at  nm indicate the face-on trimer separation measured for chemoreceptor lattices [19], [22]. For ease of comparison, the zero energy for each curve was set at the tip-on configuration. For (A) we set  and for (B) we used the monolayer thickness  nm corresponding to the E. coli cytoplasmic membrane. All trimer interaction energies were calculated as in Fig. 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263354&req=5

pcbi-1003932-g003: Gateway to assembly of face-on trimer configuration.Calculated elastic interaction energy between two chemoreceptor trimers as a function of trimer orientation (upper axes) and center-to-center trimer distance (lower axes), and (A) membrane thickness and (B) membrane tension. Trimer configurations are rotated from the tip-on to the face-on configuration while maintaining reflection symmetry and a minimum edge-to-edge separation of nm, which yields the face-on trimer configuration at nm (and the tip-on trimer configuration at nm). The vertical lines at nm indicate the face-on trimer separation measured for chemoreceptor lattices [19], [22]. For ease of comparison, the zero energy for each curve was set at the tip-on configuration. For (A) we set and for (B) we used the monolayer thickness nm corresponding to the E. coli cytoplasmic membrane. All trimer interaction energies were calculated as in Fig. 2.
Mentions: Fig. 2 implies a scenario for the assembly of chemoreceptor lattices in which the tip-on trimer configuration is a gateway state yielding attraction between chemoreceptor trimers over several nanometers, with the directionality of membrane-mediated interactions ensuring that, at small separations, trimers are arranged in the face-on orientation allowing further stabilization through direct protein interactions mediated by CheA and CheW [19], [20]. In particular, the interaction potentials in Fig. 2 suggest that the face-on trimer configuration found in chemoreceptor lattices [19], [20] could be achieved through the sequence of gateway states shown in Fig. 3. For large , the tip-on configuration is strongly favored (for ease of visualization, the tip-on configuration is set as the zero of in Fig. 3). As the trimer separation shrinks below the steric constraint on the tip-on configuration, the membrane deformation energy can be lowered further by a symmetric rotation of the chemoreceptor trimers (S1 Video), ultimately yielding the observed face-on trimer configuration [19], [20] as the lowest-energy configuration, thus ensuring correct assembly of chemoreceptor lattices. Consistent with the results in Fig. 2, we find that the membrane-mediated interactions stabilizing the sequence of gateway states in Fig. 3 vanish for lipid bilayers matching the chemoreceptor hydrophobic thickness and increase with the magnitude of the hydrophobic mismatch (Fig. 3A). Similarly, our model predicts that the reduction in membrane deformation energy associated with the sequence of gateway states in Fig. 3 increases with increasing membrane tension (Fig. 3B).

Bottom Line: In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers.Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties.Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers.

View Article: PubMed Central - PubMed

Affiliation: Departments of Physics & Astronomy and Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

ABSTRACT
In vivo fluorescence microscopy and electron cryo-tomography have revealed that chemoreceptors self-assemble into extended honeycomb lattices of chemoreceptor trimers with a well-defined relative orientation of trimers. The signaling response of the observed chemoreceptor lattices is remarkable for its extreme sensitivity, which relies crucially on cooperative interactions among chemoreceptor trimers. In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers. Here we introduce a biophysical model of bilayer-chemoreceptor interactions, which allows us to quantify the role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices. We find that, even in the absence of direct protein-protein interactions, membrane-mediated interactions can yield assembly of chemoreceptor lattices at very dilute trimer concentrations. The model correctly predicts the observed honeycomb architecture of chemoreceptor lattices as well as the observed relative orientation of chemoreceptor trimers, suggests a series of "gateway" states for chemoreceptor lattice assembly, and provides a simple mechanism for the localization of large chemoreceptor lattices to the cell poles. Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties. Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers.

Show MeSH
Related in: MedlinePlus