membranbinding

Membranbinding refers to the association of biomolecules with cellular membranes. It encompasses reversible, non-covalent interactions as well as covalent attachments that localize proteins or other molecules to membranes. Membranbinding can involve peripheral associations with the membrane surface, transient insertion into one leaflet, or permanent incorporation via transmembrane domains or covalent lipid modifications.

Non-covalent mechanisms include electrostatic interactions between basic protein regions and negatively charged lipids such as phosphatidylserine and phosphoinositides, hydrogen bonding, and hydrophobic interactions with lipid acyl chains. Amphipathic helices can insert shallowly into one leaflet. Covalent lipidation, including myristoylation, palmitoylation, and prenylation, anchors proteins more stably. Specific lipid-binding domains (PH, C2, ENTH, PX, BAR) confer selective membrane affinity for particular lipid species.

Issues of regulation and specificity: lipid composition, membrane curvature, and calcium can modulate membranbinding. Reversible binding allows rapid relocalization during signaling; phosphorylation or other post-translational modifications can alter affinity or localization. Localization to membranes can influence protein activity and interactions, creating feedback in signaling networks.

Physiological roles and examples: membranbinding governs signaling cascades, vesicle trafficking, cytoskeletal organization, and membrane remodeling. Examples include Ras family proteins that localize to the plasma membrane via covalent lipid modification; annexins that bind membranes in a Ca2+-dependent manner; and many kinases or adaptors recruited to PIP-rich membranes by PH domains.

Experimental approaches: liposome-binding assays and co-sedimentation measure affinity to membranes; surface plasmon resonance and fluorescence-based methods quantify kinetics; live-cell imaging tracks membrane recruitment. Challenges include capturing transient interactions and distinguishing membrane-binding from full insertion or transmembrane integration.