Mutational analysis of these tryptophans and of this region in general suggests that it plays a crucial, nonredundant role in membrane fusion ( 39, 53). Approximately half of the residues are hydrophobic, with five being tryptophan. This region is one of the most highly conserved sequence stretches in the envelope ectodomain ( 25, 68). The membrane-proximal region of the gp41 ectodomain spans roughly 30 residues, ending at Lys 683 (HXBc2 numbering) immediately upstream of the transmembrane domain, and encompasses the 2F5, 4E10, and Z13 epitopes. Although the three neutralize at different capacities, with 2F5 being the most potent, 4E10 being the most broad, and Z13 being the least potent or broad, the fact that all three bind to the same continuous membrane-proximal region of gp41 ( 68) suggests that unlike anti-gp120 broadly neutralizing antibodies, which bind to disparate regions of gp120, these antibodies may be less unique or difficult to elicit. The anti-gp41 broadly neutralizing antibodies, 2F5, 4E10, and Z13, have also proven scarce, but for reasons that are less clear. Of the antibodies directed against gp120, 2G12 recognizes a carbohydrate epitope on gp120 in a way which requires its domains to be swapped ( 7), and b12 must bypass conformational masking of the CD4-binding site ( 28, 54). The scarcity of these broadly neutralizing antibodies, however, may be a result of the unique characteristics through which they neutralize. Study of these antibodies has provided insight into which regions of HIV might be vulnerable to the immune system and, in some cases, through what mechanism. Indeed, only five broadly neutralizing HIV-1-reactive monoclonal antibodies have thus far been isolated two (2G12 and b12) are directed against the HIV-1 exterior gp120 envelope glycoprotein ( 47, 51, 60, 61), and the other three (2F5, 4E10, and Z13) are directed against the transmembrane gp41 envelope glycoprotein ( 40, 41, 49, 57, 68). Infection by HIV-1 generates many antibodies, but most of these are nonneutralizing ( 63) or are easily bypassed by minor viral changes ( 50, 62). Of primary concern in recent efforts to develop a vaccine against human immunodeficiency virus type 1 (HIV-1) has been the design of immunogens that have the capacity to elicit potently neutralizing antibodies which are effective against a wide spectrum of HIV-1 strains. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. The structures reveal an extended gp41 conformation, which stretches over 30 Å in length. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-Å resolutions, respectively. APRs filter out contaminated from the air, while SARs give you clean air supplied by a tank.īrowse our selection of face masks, respirators and filters, or find more health and safety gear in our eye protection, ear protection and headwear ranges.The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. Respirators come in different class bands, depending on the environment: air-purifying respirators (APRs) and supplied-air respirators (SARs). Our face and dust masks cover a range of styles for various workplaces. Go for a full mask if you want added protection for eyes and face, or get a more flexible half mask that covers the mouth or lower part of the head. Quality respiratory protection is essential to ensuring good health and safety in the workplace, with many maintenance, building, mechanical, and industrial cleaning sectors requiring staff to wear face masks everyday.Īt MI Supplies, we have a variety of full and half face masks, expertly designed to fit securely on your head using a comfortable elasticated strap.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |