ArticleProceedings of the National Academy of Sciences of the United States of America2014
A frequent, GxxxG-mediated, transmembrane association motif is optimized for the formation of interhelical Cα-H hydrogen bonds.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 109 citations in OpenAlex.
- Chain-Length Regulation by WzzE Is Necessary for, but Genetically Separable From, Cyclic Enterobacterial Common Antigen Synthesis.Molecular microbiology · 2026Article
- Backbone Nitrogen Substitution Probes the Role of Glycine Residues at GxxxG Interfaces in Transmembrane Helices.Biochemistry · 2026Article
- Packing of apolar amino acids is not a strong stabilizing force in transmembrane helix dimerization.Biophysical journal · 2025Article
- Design principles of the common Gly-X6-Gly membrane protein building block.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- Comprehensive Analysis of the GXXXG Motif Reveals Structural Context-Dependent Diversity and Composition Across Proteins.International journal of molecular sciences · 2025Article
- STIM1 transmembrane helix dimerization captured by AI-guided transition path sampling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
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- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1.Biological chemistry · 2024Article
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- A Rigorous Framework for Calculating Protein-Protein Binding Affinities in Membranes.Journal of chemical theory and computation · 2023Article
- 'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.Biomedicines · 2023Review
- Mechanosensitive aquaporins.Biophysical reviews · 2023Review
- GxxxG Motif Stabilize Ion-Channel like Pores through CInternational journal of molecular sciences · 2023Article
- Thermodynamic analysis of the GASBiophysical journal · 2023Article
- Formation of extramembraneProceedings of the National Academy of Sciences of the United States of America · 2022Article
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Carbon hydrogen bonds between Cα-H donors and carbonyl acceptors are frequently observed between transmembrane helices (Cα-H···O=C). Networks of these interactions occur often at helix-helix interfaces mediated by GxxxG and similar patterns. Cα-H hydrogen bonds have been hypothesized to be important in membrane protein folding and association, but evidence that they are major determinants of helix association is still lacking. Here we present a comprehensive geometric analysis of homodimeric helices that demonstrates the existence of a single region in conformational space with high propensity for Cα-H···O=C hydrogen bond formation. This region corresponds to the most frequent motif for parallel dimers, GASright, whose best-known example is glycophorin A. The finding suggests a causal link between the high frequency of occurrence of GASright and its propensity for carbon hydrogen bond formation. Investigation of the sequence dependency of the motif determined that Gly residues are required at specific positions where only Gly can act as a donor with its "side chain" Hα. Gly also reduces the steric barrier for non-Gly amino acids at other positions to act as Cα donors, promoting the formation of cooperative hydrogen bonding networks. These findings offer a structural rationale for the occurrence of GxxxG patterns at the GASright interface. The analysis identified the conformational space and the sequence requirement of Cα-H···O=C mediated motifs; we took advantage of these results to develop a structural prediction method. The resulting program, CATM, predicts ab initio the known high-resolution structures of homodimeric GASright motifs at near-atomic level.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.