Anchoring mechanisms of membrane-associated M13 major coat protein

Stopar, David; Spruijt, Ruud B.; Hemminga, M.A.

doi:10.1016/j.chemphyslip.2006.02.023

Cited by 38 publications

(53 citation statements)

References 77 publications

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“…Serum Abs did not neutralize HIV-1, although the immunogens were shown to inhibit viral entry, suggesting that this proteoliposome may have potential therapeutic qualities (124). This example shows that liposomes may present the MPER in the context of membrane; however, it may be important to optimize lipid content, as bilayer thickness can alter the tilt of a TM helix, potentially affecting antigen display (114,219). This approach will require further optimization to confirm whether or not liposomes are an effective carrier for the MPER.…”

Section: Should Mper-targeting Vaccines Be Presented In the Context Omentioning

confidence: 99%

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

Montero¹,

Houten

Wang³

et al. 2008

Microbiol Mol Biol Rev

234

194

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SUMMARY Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented.

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Section: Should Mper-targeting Vaccines Be Presented In the Context Omentioning

confidence: 99%

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

Montero¹,

Houten

Wang³

et al. 2008

Microbiol Mol Biol Rev

234

194

View full text Add to dashboard Cite

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“…4). Since aromatic amino acids, including phenylalanine, are frequently utilized for membrane anchoring (24,34,37,38,41), the hydrophobicity of the six-member ring structure is assumed to be critical for ITM-mediated B7-2 downregulation. This hypothesis was supported by site saturation mutagenesis of Phe119; tyrosine, which also contains a six-member ring structure, could function instead of phenylalanine at position 119.…”

Section: Discussionmentioning

confidence: 99%

The Intertransmembrane Region of Kaposi's Sarcoma-Associated Herpesvirus Modulator of Immune Recognition 2 Contributes to B7-2 Downregulation

Kajikawa

Gotō

et al. 2012

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor virus, encodes two homologous membrane-associated E3 ubiquitin ligases, modulator of immune recognition 1 (MIR1) and MIR2, to evade host immunity. Both MIR1 and MIR2 downregulate the surface expression of major histocompatibility complex class I (MHC I) molecules through ubiquitin-mediated endocytosis followed by lysosomal degradation. Since MIR2 additionally downregulates a costimulatory molecule (B7-2) and an integrin ligand (intercellular adhesion molecule 1 [ICAM-1]), MIR2 is thought to be a more important molecule for immune evasion than MIR1; however, the molecular basis of the MIR2 substrate specificity remains unclear. To address this issue, we determined which regions of B7-2 and MIR2 are required for MIR2-mediated B7-2 downregulation. Experiments with chimeras made by swapping domains between human B7-2 and CD8α, a non-MIR2 substrate, and between MIR1 and MIR2 demonstrated a significant contribution of the juxtamembrane (JM) region of B7-2 and the intertransmembrane (ITM) region of MIR2 to MIR2-mediated downregulation. Structure prediction and mutagenesis analyses indicate that Phe119 and Ser120 in the MIR2 ITM region and Asp244 in the B7-2 JM region contribute to the recognition of B7-2 by MIR2. This finding provides new insight into the molecular basis of substrate recognition by MIR family members.

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“…It is significant that many membrane-spanning proteins have bands of aromatic and/or positively charged residues at the membrane interface, which could serve as anchors for the protein orientation and promote favorable protein-lipid interactions. This anchoring is a widespread characteristic that is observed for a variety of proteins having both ␣ and ␤ transmembrane folds (1)(2)(3)(4)(5). Furthermore, polar amino acids influence the topology of membrane proteins as the direction of insertion is driven by the asymmetric positioning of basic residues (Lys and Arg), giving rise to the "positive inside" rule for helical membrane proteins (6).…”

mentioning

confidence: 99%

Charged or Aromatic Anchor Residue Dependence of Transmembrane Peptide Tilt

Vostrikov

Daily

Greathouse

et al. 2010

Journal of Biological Chemistry

185

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The membrane-spanning segments of integral membrane proteins often are flanked by aromatic or charged amino acid residues, which may "anchor" the transmembrane orientation. Single spanning transmembrane peptides such as those of the WALP family, acetyl-GWW(LA) n LWWA-amide, furthermore adopt a moderate average tilt within lipid bilayer membranes. To understand the anchor residue dependence of the tilt, we introduce Leu-Ala "spacers" between paired anchors and in some cases replace the outer tryptophans. The resulting peptides, acetyl-GX 2 ALW(LA) 6 LWLAX 22 A-amide, have Trp, Lys, Arg, or Gly in the two X positions. The apparent average orientations of the core helical sequences were determined in oriented phosphatidylcholine bilayer membranes of varying thickness using solid-state 2 H NMR spectroscopy. When X is Lys, Arg, or Gly, the direction of the tilt is essentially constant in different lipids and presumably is dictated by the tryptophans (Trp 5 and Trp 19 ) that flank the inner helical core. The Leu-Ala spacers are no longer helical. The magnitude of the apparent helix tilt furthermore scales nicely with the bilayer thickness except when X is Trp. When X is Trp, the direction of tilt is less well defined in each phosphatidylcholine bilayer and varies up to 70°among 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, and 1,2-dilauroylsn-glycero-3-phosphocholine bilayer membranes. Indeed, the X ‫؍‬ Trp case parallels earlier observations in which WALP family peptides having multiple Trp anchors show little dependence of the apparent tilt magnitude on bilayer thickness. The results shed new light on the interactions of arginine, lysine, tryptophan, and even glycine at lipid bilayer membrane interfaces.The lipid bilayer environment has a profound influence on the properties of peptides and proteins found within it. It is significant that many membrane-spanning proteins have bands of aromatic and/or positively charged residues at the membrane interface, which could serve as anchors for the protein orientation and promote favorable protein-lipid interactions. This anchoring is a widespread characteristic that is observed for a variety of proteins having both ␣ and ␤ transmembrane folds (1-5). Furthermore, polar amino acids influence the topology of membrane proteins as the direction of insertion is driven by the asymmetric positioning of basic residues (Lys and Arg), giving rise to the "positive inside" rule for helical membrane proteins (6). Little is known, nevertheless, about the contributions of these residues in defining the orientations of the transmembrane segments within lipid bilayers (7).Due to the inherent complexity of membrane proteins in the native biological membrane environment, model systems provide meaningful ways to address specific questions about protein/lipid interactions. In particular, model peptides of the WALP family, having the general sequence acetyl-GWW-(LA) n LWWA- [ethanol]amide, have yielded valuable information about peptide orientations, dynam...

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Anchoring mechanisms of membrane-associated M13 major coat protein

Cited by 38 publications

References 77 publications

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

The Intertransmembrane Region of Kaposi's Sarcoma-Associated Herpesvirus Modulator of Immune Recognition 2 Contributes to B7-2 Downregulation

Charged or Aromatic Anchor Residue Dependence of Transmembrane Peptide Tilt

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