Lipids in the periprotein environment: an under-explored link in the lipid-central dogma crosstalk
Year: 2026
Type: article
Abstract: Protein function is determined not only by its sequence, structure and partners, but also by the surrounding physicochemical environment comprising lipids, metabolites, ions and other macromolecules – hereby collectively referred to as the ‘periprotein environment’. Among these factors, the periprotein lipidome is emerging as an active functional matrix that shapes protein organization, conformational dynamics, assembly and activity. Here we summarize recent evidence demonstrating the functional crosstalk between the periprotein lipidome and the hosted proteins, focusing on hydrophobic proteins that are membrane-resident or are associated with lipid assemblies including vesicles, droplets and lipoproteins. We discuss examples ranging from defined lipid-binding pockets that allosterically regulate membrane-protein conformations to collective annular lipid environments that tune protein topology, multimerization and activity. These co-adaptations are driven by forces including hydrophobic compatibility, electrostatic attractions, hydrogen bonds, and van der Waals interactions, etc . Furthermore, we discuss current methods to profile the periprotein lipidomes, pinpoint the technical challenges, and posit alternative strategies to address this gap. As an under-explored link for understanding the principles underlying the lipid-central dogma crosstalk in life, we advocate for systematic characterizations of the periprotein lipidome for diverse target proteins and in various pathophysiological contexts.
Source: Fundamental Research
Authors: Zhibin Li, Yang Lu, Yilong Zou
Institution: Westlake University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G5196134038, G6020955475
OpenAlex ID: W7207538818