Trends in Biochemical Sciences
ReviewMembrane curvature and its generation by BAR proteins
Section snippets
Membrane curvature: a vital property of cells
Separation of ‘inside’ from ‘outside’ was a pivotal event in the creation of life; it happened when organic amphiphiles, known as phospholipids, became abundant enough to form self-sealing, curved and semipermeable barriers that established chemically defined compartments. The same breakthrough, however, created many challenges because the newly formed flexible envelopes, known as biological membranes, needed to allow the steady influx of nutrients and the secretion of wastes. Moreover, cells
Architecture and classification of BAR domain proteins
Among the plethora of membrane-bending proteins, the superfamily of BAR proteins has become a main focus of attention over recent years. Numerous reports reaffirm the notion that these proteins belong to an essential arsenal that cells deploy to shape membranes from yeast to mammals (see [14] for a review). Lacking characteristic signature sequence motifs in their primary structure, membership in the BAR domain superfamily is not readily recognizable. However, at the structural level BAR
Molecular mechanisms of membrane bending
In the past, crystal structures and molecular dynamics simulations have strongly influenced how the field thinks about membrane bending by BAR domains [20]. Among the most intuitive implications arising from the structures was the hypothesis that the intrinsic curvature of BAR domain dimers aids membrane remodeling by simply imposing its shape on the membrane substrate (Figure 1b, upper panel). This mode of action has become known as the ‘scaffolding’ mechanism 13, 41 and is well supported by
Visualizing membrane-bound scaffolds: the new frontier
Complementing high-resolution structural and spectroscopic studies, electron microscopic reconstructions of membrane-bound F-BAR and N-BAR proteins have emerged over the past 4 years 17, 51. These reconstructions confirmed the scaffolding and wedging mechanisms, and for the first time revealed design details of a few select lattices that BAR domains are capable of forming on the surface of membranes. Although the helical arrays used for these studies were more extensive, and probably more
Control of membrane binding
The ability of BAR domains to engage bilayers and recruit specific interaction partners creates a need to control when and where a given BAR domain protein can gain access to its targets. A crucial parameter for controlling membrane access is membrane curvature. Numerous studies have shown that BAR proteins have a preference for membranes with specific curvatures in vitro, and that the curvature preferences correlate with the intrinsic curvature of the BAR domain 19, 44, 49. Adding to this
Recruitment of BAR protein interacting proteins
As the structures of BAR domain scaffolds begin to emerge, new and puzzling observations take center stage. For instance, the experimentally determined lattice structures allow estimation of the actual concentrations of SH3 or other interactor domains that are tethered to the membrane surface through the BAR lattice. The results of a ‘back of the envelope’ calculation yields a surprising result: assuming a 100-nm annulus above the membrane surface, the concentrations of interactor domains are
Concluding remarks
Curvature and its generation is a rapidly expanding field in membrane biochemistry and biophysics. The past few years have seen dramatic improvements in the structure determination of membrane-bound scaffolds, information technology, and the development of suitable models that allow the systematic study of membrane remodeling in living organisms. The original, simplistic view that differences in intrinsic curvatures define the spatial and temporal patterns of BAR domain protein deployment [74]
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