Wobbly backbone: The backbone dynamics of the amyloid precursor protein (APP) transmembrane helix was compared to those of other transmembrane domains. In contrast to expectation, no above-average backbone dynamics was found for the APP transmembrane helix; the dynamics thus appears not to be optimized for cleavage.
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http://dx.doi.org/10.1002/cbic.201300322 | DOI Listing |
Int J Mol Sci
January 2025
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.
Alzheimer's disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the APP and secretase location relative to ordered or disordered membrane microdomains. We used high-resolution NMR to probe the interactions of the cholesterol analog with APP transmembrane domain in two membrane-mimicking systems resembling ordered or perturbed lipid environments (bicelles/micelles).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Faculty of Life Sciences and Medicine, Harbin Institute of Technology Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
Lysophosphatidic acid (LPA) exerts its physiological roles through the endothelialdifferentiation gene (EDG) family LPA receptors (LPAR1-3) or the non-EDG family LPA receptors (LPAR4-6). LPAR6 plays crucial roles in hair loss and cancer progression, yet its structural information is very limited. Here, we report the cryoelectron microscopy structure of LPA-bound human LPAR6 in complex with a mini G or G protein.
View Article and Find Full Text PDFNat Commun
January 2025
NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal. Electronic address:
The adenosine A receptor (AR), a class A GPCR, is a known player in neurological diseases, including Parkinson's disease and Alzheimer's disease, and is also implicated in SARS-CoV-2 infection. Recent studies have revealed its oligomerization with metabotropic glutamate receptor type 5 (mGluR), a class C G protein coupled receptor (GPCR) that exists in the homodimeric form. Simultaneous activation of both receptors synergistically enhances mGluR-mediated effects in the hippocampus.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Key Laboratory of RNA Innovation, Science, and Engineering; Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly.
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