Effects of Nicotine on the Thermodynamics and Phase Coexistence of Pulmonary Surfactant Model Membranes.

Phase separation is essential for membrane function, and alterations in phase coexistence by membrane-interacting molecules, such as nicotine, can impair membrane stability. With the increasing use of e-cigarettes, concerns have arisen about the impact of nicotine on pulmonary surfactants. Here, we used differential scanning calorimetry (DSC), molecular dynamics (MD) simulations, and electron spin resonance (ESR) to examine nicotine's effect on the phase coexistence of two surfactant models: pure DPPC and a DPPC/POPC/POPG mixture.

Resurrecting Golgi proteins to grasp Golgi ribbon formation and self-association under stress.

The Golgi complex is an essential organelle of the eukaryotic exocytic pathway. A subfamily of Golgi matrix proteins, called GRASPs, is central in stress-induced unconventional secretion, Golgi dynamics during mitosis/apoptosis, and Golgi ribbon formation. The Golgi ribbon is vertebrate-specific and correlates with the appearance of two GRASP paralogues and two Golgins (GM130/Golgin45), which form specific GRASP-Golgin pairs.

Structural and thermodynamic analyses of human TMED1 (p24γ1) Golgi dynamics.

The transmembrane emp24 domain-containing (TMED) proteins, also called p24 proteins, are members of a family of sorting receptors present in all representatives of the Eukarya and abundantly present in all subcompartments of the early secretory pathway, namely the endoplasmic reticulum (ER), the Golgi, and the intermediate compartment. Although essential during the bidirectional transport between the ER and the Golgi, there is still a lack of information regarding the TMED's structure across different subfamilies. Besides, although the presence of a TMED homo-oligomerization was suggested previously based on crystallographic contacts observed for the isolated Golgi Dynamics (GOLD) domain, no further analyses of its presence in solution were done.

Myristoylation and its effects on the human Golgi Reassembly and Stacking Protein 55.

GRASP55 is a myristoylated protein localized in the medial/trans-Golgi faces and involved in the Golgi structure maintenance and the regulation of unconventional secretion pathways. It is believed that GRASP55 achieves its main functionalities in the Golgi organization by acting as a tethering factor. When bound to the lipid bilayer, its orientation relative to the membrane surface is restricted to determine its proper trans-oligomerization.

Conformational flexibility of GRASPs and their constituent PDZ subdomains reveals structural basis of their promiscuous interactome.

The Golgi complex is a central component of the secretory pathway, responsible for several critical cellular functions in eukaryotes. The complex is organized by the Golgi matrix that includes the Golgi reassembly and stacking protein (GRASP), which was shown to be involved in cisternae stacking and lateral linkage in metazoan. GRASPs also have critical roles in other processes, with an unusual ability to interact with several different binding partners.

Exploring Conformational Transitions and Free-Energy Profiles of Proton-Coupled Oligopeptide Transporters.

Proteins involved in peptide uptake and transport belong to the proton-coupled oligopeptide transporter (POT) family. Crystal structures of POT family members reveal a common fold consisting of two domains of six transmembrane α helices that come together to form a "V" shaped transporter with a central substrate binding site. Proton-coupled oligopeptide transporters operate through an alternate access mechanism, where the membrane transporter undergoes global conformational changes, alternating between inward-facing (IF), outward-facing (OF), and occluded (OC) states.

Conformational Diversity of the Helix 12 of the Ligand Binding Domain of PPARγ and Functional Implications.

Nuclear hormone receptors (NR) are transcription factors that activate gene expression in response to ligands. Structural and functional studies of the ligand binding domains (LBD) of NRs revealed that the dynamics of their C-terminal helix (H12) is fundamental for NR activity. H12 is rigid and facilitates binding of coactivator proteins in the agonist-bound LBD.

Dynamics of nuclear receptor Helix-12 switch of transcription activation by modeling time-resolved fluorescence anisotropy decays.

Nuclear hormone receptors (NRs) are major targets for pharmaceutical development. Many experiments demonstrate that their C-terminal Helix (H12) is more flexible in the ligand-binding domains (LBDs) without ligand, this increased mobility being correlated with transcription repression and human diseases. Crystal structures have been obtained in which the H12 is extended, suggesting the possibility of large amplitude H12 motions in solution.