Membrane curvature is essential to diverse cellular functions. While classically attributed to structured domains, recent work illustrates that intrinsically disordered proteins are also potent drivers of membrane bending. Specifically, repulsive interactions among disordered domains drive convex bending, while attractive interactions drive concave bending, creating membrane-bound, liquid-like condensates. How might disordered domains that contain both repulsive and attractive domains affect curvature? Here, we examined chimeras that combined attractive and repulsive interactions. When the attractive domain was closer to the membrane, its condensation amplified steric pressure among repulsive domains, leading to convex curvature. In contrast, when the repulsive domain was closer to the membrane, attractive interactions dominated, resulting in concave curvature. Further, a transition from convex to concave curvature occurred with increasing ionic strength, which reduced repulsion while enhancing condensation. In agreement with a simple mechanical model, these results illustrate a set of design rules for membrane bending by disordered proteins.

The ability of proteins to generate curved membrane structures is essential to diverse cellular functions, from membrane traffic to nuclear transport. Established mechanisms of membrane bending require protein domains with specific structural features such as curved scaffolds and wedge-like amphipathic helices. However, recent work has shown that intrinsically disordered proteins, which lack a well-defined secondary structure, can also be potent drivers of membrane curvature. Specifically, steric pressure among membrane-bound disordered domains that repel one another can drive convex bending. In contrast, disordered domains that attract one another, forming liquid-like condensates, can drive concave bending by compressing membrane surfaces. How might disordered domains that contain both repulsive and attractive domains impact membrane curvature? Here we examine a series of recombinant chimeras that link attractive and repulsive domains within the same, membrane-bound protein. When the attractive domain was closer to the membrane, condensation of these domains helped to concentrate the repulsive domains, amplifying steric pressure, leading to convex curvature. In contrast, when the order of the attractive and repulsive domains was reversed, such that the repulsive domain was closer to the membrane surface, attractive interactions dominated, resulting concave curvature. Further, a transition from convex to concave curvature was observed when an increase in ionic strength was used to simultaneously reduce steric clashes among the repulsive domains while increasing condensation of the attractive domains. Collectively, these results illustrate a set of design rules that can be used to control membrane curvature by adjusting the balance between attractive and repulsive interactions among disordered proteins.

No abstract

No abstract