Motifs of serine and threonine can drive association of transmembrane helices

Dawson, Jessica; Weinger, Joshua S.; Engelman, Donald M.

doi:10.1006/jmbi.2001.5353

Cited by 231 publications

(236 citation statements)

References 28 publications

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“…In the case of Yang et al there is background activation of downstream signaling molecules, but the activation levels with a ligand were much higher than those without a ligand (Yang et al 1998). In this case, the chimeric receptor lacks the transmembrane domain which significantly contributes to interchain interaction of receptor chains (Dawson et al 2002). These previous reports are consistent with our notion that the conformation and interchain interaction of the receptor complex are key determinants for the signaling properties of cytokine receptors (Kawahara et al 2004b;Liu et al 2008).…”

Section: Discussionsupporting

confidence: 79%

Construction of antibody/insulin receptor chimera for growth induction of mammalian cells

et al. 2013

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The insulin receptor (IR) is expressed ubiquitously in various tissues, where insulin exerts various biological effects on the target cells, such as cellular metabolic changes, cell proliferation and differentiation. Therefore, mimicry of insulin signaling would be a promising strategy to realize artificial control of such cellular fates. In this study, we constructed an antibody/insulin receptor chimera that enables to utilize any antigen as the ligand in principle. We constructed chimeric receptors consisting of antifluorescein single chain Fv (scFv), the extracellular D2 domain of erythropoietin receptor and the transmembrane/intracellular domains of IR (scFv-IR; S-IR). The function of S-IR was evaluated in terms of growth signal transduction in murine pro-B Ba/F3 cells and murine fibroblast NIH/3T3 cells. S-IR exerted IL-3-independent cell growth in Ba/F3 cells, while NIH/ 3T3 cells expressing S-IR acquired growth advantage over parental NIH/3T3 cells in a low-serum condition. S-IR induced phosphorylation of S-IR itself and key signaling molecules downstream of IR. Although antigen-independent activation was significantly observed, S-IR enabled specific amplification of the gene-transduced cells.

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Section: Discussionsupporting

confidence: 79%

Construction of antibody/insulin receptor chimera for growth induction of mammalian cells

et al. 2013

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“…This would be consistent with our results that show the disulfide bond is disrupted in both G128L and G132L and that direct interaction between TMD2 and TMD5 is disrupted in those mutant carboxylases. A likely candidate for the other TMD involved would be TMD4, since it has five serine residues which are common in sequences identified as supporting TMD associations (42). However, since we only modeled TMDs 2 and 5, our homology construct does not constitute the entire neighborhood of G128 and G132; therefore, it is somewhat difficult to predict the outcome of G128L and/or G132L mutations with the current model.…”

Section: Analysis Of the Homology Model In The Context Of Our Experimmentioning

confidence: 99%

Transmembrane Domain Interactions and Residue Proline 378 Are Essential for Proper Structure, Especially Disulfide Bond Formation, in the Human Vitamin K-Dependent γ-Glutamyl Carboxylase

et al. 2008

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We used recombinant techniques to create a two-chain form (residues 1-345 and residues 346-758) of the vitamin K-dependent γ-glutamyl carboxylase, a glycoprotein located in the endoplasmic reticulum containing five transmembrane domains. The two-chain carboxylase had carboxylase and epoxidase activities similar to those of one-chain carboxylase. In addition, it had normal affinity for the propeptide of factor IX. We employed this molecule to investigate formation of the one disulfide bond in carboxylase, the transmembrane structure of carboxylase, and the potential interactions among the carboxylase's transmembrane domains. Our results indicate that the two peptides of the two-chain carboxylase are joined by a disulfide bond. Proline 378 is important for the structure necessary for disulfide formation. Results with the P378L carboxylase indicate that noncovalent bonds maintain the two-chain structure even when the disulfide bond is disrupted. As we had previously proposed, the fifth transmembrane domain of carboxylase is the last and only transmembrane domain in the C-terminal peptide of the two-chain carboxylase. We show that the noncovalent association between the two chains of carboxylase involves an interaction between the fifth transmembrane domain and the second transmembrane domain. Results of a homology model of transmembrane domains 2 and 5 suggest that not only do these two domains associate but that transmembrane domain 2 may interact with another transmembrane domain. This latter interaction may be mediated at least in part by a motif of glycine residues in the second transmembrane domain.The vitamin K-dependent γ-glutamyl carboxylase is a 758-residue integral membrane glycoprotein of the endoplasmic reticulum (ER). 1 It catalyzes the posttranslational modification of specific glutamic acid residues of vitamin K-dependent proteins to γ-carboxyglutamic acid residues. This posttranslational modification is critical for the biological † This work was supported by National Institutes of Health (NIH) Grant HL48318 (to D.W.S.) and by the Intramural Research Program of the NIH and NIEHS (to L.P.).*Author to whom correspondence should be addressed. Phone: 919-962-2267. Fax: 919-962-9266. jktie@email.unc.edu. ‡ University of North Carolina at Chapel Hill. § National Institute of Environmental Health Sciences, NIH.1 Abbreviations: ER, endoplasmic reticulum; TMD, transmembrane domain; NEM, CHAPS,dimethylammonio]-1-propanesulfonate; DTT, dithiothreitol; MOPS, 3-(N-morpholino)propanesulfonic acid (4-morpholinepropanesulfonic acid); MES, 2-(N-morpholino)ethanesulfonic acid (4-morpholineethanesulfonic acid); vitamin K 1(20) , 2-methyl-3-phytyl-1,4-naphthoquinone; PNGase F, peptide:N-glycosidase F; proFIX, 19 amino acid peptide comprising residues TVFLDHENANKILNRPKRY of human profactor IX; SRII, sensory rhodopsin II; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene fluoride.

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“…In wt LH2, there are a number of residues that interact both with ␣-BChl-B850 and ␤-BChl-B850 at a radius of Յ4 Å (33). In such "three-body" interactions, which have been proposed to be a significant factor for the stability of membrane proteins (19), residues with short side chains, in particular serine residues, are frequently found (19,22). In addition to the specific residues participating in the three-body interaction, the sequence context in the vicinity seems to be essential for maintaining the stabilizing effects of such clusters (19).…”

Section: Fig 3 Optical Absorption and CD Spectra Of Wt Lh2 (-) Lh2mentioning

confidence: 99%

“…In addition, in numerous high resolution structures of membrane proteins, hydrogen bonding networks are likely to exist at helix-helix interfaces between membrane-embedded backbone keto groups and polar side chains as well as between side chain groups (19 -21). Particular hydrogen bonding motifs have been identified in which residues with short side chains, especially serine, are frequently found, but also histidine and tyrosine are often present in these motifs (20,22).…”

mentioning

confidence: 99%

Hydrogen Bonding in a Model Bacteriochlorophyll-binding Site Drives Assembly of Light Harvesting Complex

Kwa¹,

García‐Martín²,

Végh

et al. 2004

Journal of Biological Chemistry

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In this study, the contribution of intramembrane hydrogen bonding at the interface between polypeptide and cofactor is explored in the native lipid environment by use of model bacteriochlorophyll proteins. In the peripheral antenna complex, LH2, large portions of the transmembrane helices, which make up the dimeric bacteriochlorophyll-binding site, are replaced by simplified, alternating alanine-leucine stretches. Replacement of either one of the two helices with the helices containing the model sequence at a time results in the assembly of complexes with nearly native light harvesting properties. In contrast, replacement of both helices results in the loss of antenna complexes from the membrane. The assembly of such doubly modified complexes is restored by a single intramembrane serine residue at position ؊4 relative to the liganding histidine of the ␣-subunit. In situ analysis of the spectral properties in a series of site-directed mutants reveals a critical dependence of the model complex assembly on the side chain of the residue at this position in the helix. A hydrogen bond between the hydroxy group of the serine and the 13 1 keto group of one of the central bacteriochlorophylls of the complexes is identified by Raman spectroscopy in the model antenna complex containing one of the alanine-leucine helices. The additional OH group of the serine residue, which participates in hydrogen bonding, increases the thermal stability of the model complexes in the native membrane. Intramembrane hydrogen bonding is thus shown to be a key factor for the binding of bacteriochlorophyll and assembly of this model cofactor-polypeptide site.

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Motifs of serine and threonine can drive association of transmembrane helices

Cited by 231 publications

References 28 publications

Construction of antibody/insulin receptor chimera for growth induction of mammalian cells

Construction of antibody/insulin receptor chimera for growth induction of mammalian cells

Transmembrane Domain Interactions and Residue Proline 378 Are Essential for Proper Structure, Especially Disulfide Bond Formation, in the Human Vitamin K-Dependent γ-Glutamyl Carboxylase

Hydrogen Bonding in a Model Bacteriochlorophyll-binding Site Drives Assembly of Light Harvesting Complex

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