Structural constraints imposed by the conserved fusion peptide on the HIV-1 gp41 epitope recognized by the broadly neutralizing antibody 2F5. 2009

Igor de la Arada, and Jean-Philippe Julien, and Beatriz G de la Torre, and Nerea Huarte, and David Andreu, and Emil F Pai, and José L R Arrondo, and José L Nieva
Biophysics Unit (CSIC-UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.

The HIV-1 gp41 epitope recognized by the broadly neutralizing 2F5 antibody has focused much attention as a suitable target in the design of peptide immunogens. Peptides mimicking the linear 2F5 epitope (2F5ep) are however intrinsically disordered, while the structural constraints existing in the cognate gp41 native structure recognized by the antibody are presently unknown. In recent reports, we have shown that core residues of the amino-terminal fusion peptide (FP) increase MAb2F5 affinity. Here, we have inferred the sequence-specific structural constraints imposed by the FP residues on the 2F5 epitope from the comparison of two hybrid peptides: HybK3, which connects through a flexible tether residues derived from 2F5ep and FP sequences, and scrHybK3, combining 2F5ep and an FP sequence with the conserved core scrambled. Circular dichroism, conventional and two-dimensional correlation infrared spectroscopy, and X-ray diffraction studies revealed specific structural features that were dependent on the exact FP sequence, namely, (i) the production with moderate low polarity of an intermediate folded structure enriched in beta-turns and alpha-helix; (ii) the existence in this intermediate of a thermotropic conformational transition taking place at ca. 18-20 degrees C, consistent with the conversion of 3(10)-helices into beta-turn conformers; and (iii) the presence of a C-terminal alpha-helix in crystals of Fab'-peptide complexes. Those features support the existence of native-like tertiary interactions between FP and 2F5 epitope residues, which might be important to recreate when developing an effective AIDS peptide vaccine.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002942 Circular Dichroism A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Circular Dichroism, Vibrational,Dichroism, Circular,Vibrational Circular Dichroism
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D013055 Spectrophotometry, Infrared Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR
D015700 HIV Envelope Protein gp41 Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING. Envelope Protein gp41, HIV,HIV Transmembrane Protein gp41,HTLV-III gp41,env Protein gp41, HIV,gp41(HIV),gp41 Envelope Protein, HIV
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures

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