{"doi":"10.3389/fmolb.2025.1669083","title":"Editorial: Protein regulation by lipids","abstract":"Crystallographic data provide vital clues into lipid-protein interactions. Haloarchaeal rhodopsins convert solar energy into ionic gradients on the cell membrane or act as light sensors to drive photomotility behavior, and are essential models to study protein regulation by lipids. For structural studies, membrane proteins are solubilized from the native membranes using detergents and then reconstituted in synthetic lipids. Bukhdruker et al. analyzed the highestquality crystallographic structures of haloarchaeal rhodopsins to investigate the direct molecular interactions between lipid hydrocarbon chains and the hydrophobic protein surface. The authors found that most structures obtained by different crystallization methods still contained tightly associated archaeal lipids, the shape of which closely matched grooves of the protein surface. These findings support the notion that the so-called annular lipids form the nearest layer of hydrophobic lipid side chains, which strongly interact with the hydrophobic protein surface and adopt the shape (straight and bent) of the preferred low-energy conformation, complementary to the given protein structure. An alternative approach to producing haloarchaeal rhodopsins for crystallographic studies is the expression of their genes in bacterial hosts (mostly Escherichia coli). Bacterial membranes differ from archaeal membranes in their lipid composition, and some haloarchaeal rhodopsin structures purified from bacterial hosts revealed non-native oligomeric compositions due to the lack of lipids that mediate the contact between protomers in native membranes. In contrast, other structures show bacterial lipids trying to fill in the same crevices in which native lipids are found. Such \"foreign\" lipid molecules could occupy protein sites, either like or unlike those in the native membrane, and therefore affect packing constraints and/or force the protein protomers to adopt incorrect conformations. The authors also discuss the use of noble gases to probe lipid-protein interactions and provide recommendations for enhancing the informativeness of structural studies.Super-resolution microscopy is another powerful approach to study lipid-protein interactions. Compartmentalization of different biochemical, biosynthetic, and signaling processes plays a fundamental role in cell function. Over the last decade, this view has been extended from subcellular organelles to single membranes and their primary components, including lipids and proteins. Super-resolution microscopy allows researchers to visualize single protein molecules and their clusters with nanoscale precision, surpassing the diffraction limit of conventional light microscopy. Super-resolution microscopy enables the study of membrane organization, membrane-bound processes, channels, and transporter dynamics at the nanoscale in living cells, coupling imaging with quantitative analysis. Diaz and Arnspang explored the pros and cons of using different techniques (summarized in an excellent Table 1), which allow visualization of single or clustered protein molecules and their organization within cell membranes, reveal how proteins or lipids organize into nanoscale domains, and how these domains change over time. These technologies have shown that membrane proteins and lipids are not randomly distributed but form dynamic, functional microdomains. Significantly, lipids can influence protein function not only through direct interactions but also by modulating other regulatory proteins. This regulatory role of lipids is particularly evident in pathophysiological processes such as hypertension. Lipids may regulate protein activity not directly, but by acting on other regulatory proteins that modulate the activity in question. Hypertension among children and adolescents has notably increased over the past two decades and is associated with an increased risk of stroke, myocardial infarction, and congestive heart failure. Protein kinases C (PKC) regulate ","journal":"Frontiers in Molecular Biosciences","year":2025,"id":558777,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8066,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299114,"name":"Elena G. Govorunova","orcid":"0000-0003-0522-9683","position":1,"is_corresponding":false},{"id":118092,"name":"Mikhail Bogdanov","orcid":"0000-0002-7176-8127","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40874061","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}