Conformational study of fragments of envelope proteins (gp120: 254–274 and gp41: 519–541) of HIV‐1 by NMR and MD simulations

Kanyalkar, Meena; Srivastava, Sudha; Saran, Anil; Coutinho, Evans C.

doi:10.1002/psc.530

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…Those results were in substantial agreement with NMR data published previously. Moreover, MD simulations of a fragment of gp120 (envelope protein of HIV-1) in DMSO reveled a b-sheet structure (95). According to the data described above, and taking into account our findings using MD simulations in DMSO as a membrane-mimic solvent, we can say that this solvent can be used either for hydrophilic or hydrophobic proteins, in agreement with the amphipathic characteristics of this solvent.…”

Section: Discussionsupporting

confidence: 76%

Predictions Suggesting a Participation of β-Sheet Configuration in the M2 Domain of the P2X7 Receptor: A Novel Conformation?

Teixeira¹,

Souza

Freitas

et al. 2009

Biophysical Journal

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Scanning experiments have shown that the putative TM2 domain of the P2X(7) receptor (P2X(7)R) lines the ionic pore. However, none has identified an alpha-helix structure, the paradigmatic secondary structure of ion channels in mammalian cells. In addition, some researchers have suggested a beta-sheet conformation in the TM2 domain of P2X(2). These data led us to investigate a new architecture within the P2X receptor family. P2X(7)R is considered an intriguing receptor because its activation induces nonselective large pore formation, in contrast to the majority of other ionic channel proteins in mammals. This receptor has two states: a low-conductance channel (approximately 10 pS) and a large pore (> 400 pS). To our knowledge, one fundamental question remains unanswered: Are the P2X(7)R channel and the pore itself the same entity or are they different structures? There are no structural data to help solve this question. Thus, we investigated the hydrophobic M2 domain with the aim of predicting the fitted position and the secondary structure of the TM2 segment from human P2X(7)R (hP2X(7)R). We provide evidence for a beta-sheet conformation, using bioinformatics algorithms and molecular-dynamics simulation in conjunction with circular dichroism in different environments and Fourier transform infrared spectroscopy. In summary, our study suggests the possibility that a segment composed of residues from part of the M2 domain and part of the putative TM2 segment of P2X(7)R is partially folded in a beta-sheet conformation, and may play an important role in channel/pore formation associated with P2X(7)R activation. It is important to note that most nonselective large pores have a transmembrane beta-sheet conformation. Thus, this study may lead to a paradigmatic change in the P2X(7)R field and/or raise new questions about this issue.

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Section: Discussionsupporting

confidence: 76%

Predictions Suggesting a Participation of β-Sheet Configuration in the M2 Domain of the P2X7 Receptor: A Novel Conformation?

Teixeira¹,

Souza

Freitas

et al. 2009

Biophysical Journal

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“…The crystal structure of this peptide bound to 4E10 verifies a helical conformation, in which the hydrophobic residues are located on one face of the helix (9). The fusogenic peptide, however, could adopt an ␣-helical shape or a ␤-sheet conformation depending on the peptide concentration and environmental factors such as type of lipids or the presence of cations (21)(22)(23)(24)(25)(26). The PTMR as well as the N-terminal regions of gp120 and gp41 contain several hydrophobic residues.…”

Section: Lwvtvyygvpvwkmentioning

confidence: 92%

The HIV-Neutralizing Monoclonal Antibody 4E10 Recognizes N-Terminal Sequences on the Native Antigen

Hager-Braun

Katinger

Tomer

2006

The Journal of Immunology

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Characterization of the epitope recognized by the broadly neutralizing anti-HIV Ab 4E10 has, heretofore, focused on a linear sequence from the gp41 pretransmembrane region (PTMR). Attempts to generate neutralizing Abs based on this linear epitope sequence have been unsuccessful. We have characterized the antigenic determinants on recombinant glycosylated full-length Ags, and nonglycosylated and truncated Ags recognized by 4E10 using epitope extraction and excision assays in conjunction with MALDI mass spectrometry. The mAb recognized the peptides 34LWVTVYYGVPVWK46 and 512AVGIGAVFLGFLGAAGSTMGAASMTLTVQAR542 located at the N-terminal region of gp120 and gp41, respectively. Immunoassays verified AV(L/M)FLGFLGAA as the gp41 epitope core. Recognition of the peptide from the gp41 PTMR was detected only in constructs in which the N termini of the mature envelope proteins were missing. In this region, the epitope core is located in the sequence 672WFDITNWLWY681. We hypothesize that the hydrophobic surface of the paratope functions as a “trap” for the viral sequences, which are responsible for insertion into the host cell membrane. As the N-terminal region of gp120, the fusogenic peptide of gp41, and the PTMR of gp41 show high sequence homology among various HIV strains, this model is consistent with the broadly neutralizing capabilities of 4E10.

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“…For HFP in aqueous solution at pH 3, liquid-state NMR data were consistent with predominantly unstructured peptide, while in organic solvents, both helical and β strand conformations have been observed [30,31]. A variety of biophysical techniques other than liquid-state NMR have been applied to study membrane-associated HFP and show helical conformation as well as β strand conformation which is associated with formation of HFP oligomers or aggregates [1,[32][33][34][35].…”

Section: Introductionmentioning

confidence: 89%

Chemical shift assignment and structural plasticity of a HIV fusion peptide derivative in dodecylphosphocholine micelles

Gabrys

Weliky

2007

Biochimica et Biophysica Acta (BBA) - Biomembranes

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A "HFPK3" peptide containing the 23 residues of the human immunodeficiency virus (HIV) fusion peptide (HFP) plus three non-native C-terminal lysines was studied in dodecylphosphocholine (DPC) micelles with 2D 1H NMR spectroscopy. The HFP is at the N-terminus of the gp41 fusion protein and plays an important role in fusing viral and target cell membranes which is a critical step in viral infection. Unlike HFP, HFPK3 is monomeric in detergent-free buffered aqueous solution which may be a useful property for functional and structural studies. H alpha chemical shifts indicated that DPC-associated HFPK3 was predominantly helical from I4 to L12. In addition to the highest-intensity crosspeaks used for the first chemical shift assignment (denoted I), there were additional crosspeaks whose intensities were approximately 10% of those used for assignment I. A second assignment (II) for residues G5 to L12 as well as a few other residues was derived from these lower-intensity crosspeaks. Relative to the I shifts, the II shifts were different by 0.01-0.23 ppm with the largest differences observed for HN. Comparison of the shifts of DPC-associated HFPK3 with those of detergent-associated HFP and HFP derivatives provided information about peptide structures and locations in micelles.

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Conformational study of fragments of envelope proteins (gp120: 254–274 and gp41: 519–541) of HIV‐1 by NMR and MD simulations

Cited by 8 publications

References 35 publications

Predictions Suggesting a Participation of β-Sheet Configuration in the M2 Domain of the P2X7 Receptor: A Novel Conformation?

Predictions Suggesting a Participation of β-Sheet Configuration in the M2 Domain of the P2X7 Receptor: A Novel Conformation?

The HIV-Neutralizing Monoclonal Antibody 4E10 Recognizes N-Terminal Sequences on the Native Antigen

Chemical shift assignment and structural plasticity of a HIV fusion peptide derivative in dodecylphosphocholine micelles

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