ArticleBiophysical journal2009
Transmembrane helix association affinity can be modulated by flanking and noninterfacial residues.
Article in Biophysical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 31 citations in OpenAlex.
- 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
- Natural selection on apical membrane antigen 1 (AMA1) of an emerging zoonotic malaria parasite Plasmodium inui.Scientific reports · 2024Article
- Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer.Structure (London, England : 1993) · 2023Article
- Hydrophobic mismatch and sequence specificity compete when transmembrane helix-helix interactions are measured with the TOXCAT assay.Frontiers in chemistry · 2022Article
- Role of Cholesterol in Transmembrane Dimerization of the ErbB2 Growth Factor Receptor.The Journal of membrane biology · 2021Article
- Characterization and Genomic Analysis of BUCT549, a Novel Bacteriophage InfectingFrontiers in microbiology · 2021Article
- What ATP binding does to the CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
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- A thermodynamic approach to alamethicin pore formation.Biochimica et biophysica acta · 2014Article
- A putative transmembrane leucine zipper of agrobacterium VirB10 is essential for t-pilus biogenesis but not type IV secretion.Journal of bacteriology · 2013Article
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- Interactions between ionizable amino acid side chains at a lipid bilayer-water interface.The journal of physical chemistry. B · 2011Article
- GxxxG motifs, phenylalanine, and cholesterol guide the self-association of transmembrane domains of ErbB2 receptors.Biophysical journal · 2011Article
- Self-association of models of transmembrane domains of ErbB receptors in a lipid bilayer.Biophysical journal · 2010Article
- Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?Cell adhesion & migrationReview
- Structure elucidation of dimeric transmembrane domains of bitopic proteins.Cell adhesion & migrationReview
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2 authors at 1 institution in 1 country.
Funding
Abstract
The GxxxG sequence motif mediates the association of transmembrane (TM) helices by providing a site of close contact between them. However, it is not sufficient for strong association. For example, both bacteriophage M13 major coat protein (MCP) and human erythrocyte protein glycophorin A (GpA) contain a GxxxG motif in their TM domains and form a homodimer, but the association affinity of MCP, measured by the ToxCAT in vivo assay, is dramatically weaker than that of GpA. Even when all interfacial residues of MCP were substituted for those of GpA (MCP-GpA), association remained significantly weaker than in GpA. Here we provide an explanation for these experimental observations using molecular dynamics simulations in an implicit membrane (IMM1-GC). The association free energies of GpA29 (GpA with 29 residues all from the wild-type sequence), GpA15p11 (GpA with 15 residues from the wild-type sequence plus 11 flanking residues from the ToxCAT construct), MCP, and MCP-GpA TM helices were calculated and compared. MCP and MCP-GpA have the same flanking residues used in the ToxCAT assay as those in GpA15p11, but the position of the flanking residues relative to the GxxxG motif is different. The calculated association free energies follow experimental observations: the association affinity of MCP-GpA falls between those of GpA15p11 and MCP wild-type. MCP exhibits an equally strong interhelical interaction in the TM domain. A major reason for the weaker association of MCP in the calculations was the noninterfacial residue Lys-40, which in the dimer structure is forced to be buried in the membrane interior. To alleviate the desolvation cost, in MCP and MCP-GpA dimers, Lys-40 gets deprotonated. A second factor that modulates association affinity is the flanking residues. Thanks to them, GpA15p11 exhibits a much stronger association affinity than GpA29. The positioning of the flanking residues is also important, as evidenced by the difference in association affinity between MCP and MCP-GpA on one hand and GpA15p11 on the other. Thus, residues outside the contact interface can exert a significant influence on transmembrane helix association affinity.
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