Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.

08:00 EDT 12th June 2019 | BioPortfolio

Summary of "Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies."

The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability. We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient. We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88. A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP. We further demonstrate that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles. The variable recognition of FP by bnAbs thus provides insights for vaccine design.


Journal Details

This article was published in the following journal.

Name: Cell host & microbe
ISSN: 1934-6069
Pages: 873-883.e5


DeepDyve research library

PubMed Articles [8991 Associated PubMed Articles listed on BioPortfolio]

CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity.

During the entry process, the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagem...

Capturing the inherent structural dynamics of the HIV-1 envelope glycoprotein fusion peptide.

The N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing the structural flexibili...

Cytoplasmic R-peptide of murine leukemia virus envelope protein negatively regulates its interaction with the cell surface receptor.

Cytoplasmic tails of envelope (Env) glycoproteins of many retroviruses inhibit their membrane fusion activity. The cytoplasmic 16-amino acid peptide of ecotropic murine leukemia virus (E-MLV) Env prot...

Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.

Somatic mutations within antibody variable and framework regions (FWR) can alter thermostability and structural flexibility, but their impact on functional potency is unclear. Here we study thermostab...

Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition.

Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand t...

Clinical Trials [2341 Associated Clinical Trials listed on BioPortfolio]

Identification of Broadly HIV-1 Neutralizing Antibodies (bNAb) in HIV-infected Patients in Mbeya, Tanzania.

In natural HIV disease, a small fraction (1-2%) of infected individuals develops exceptionally high titres of HIV-1 neutralizing serum activity. Antibodies isolated from these individuals ...

Evaluating the Impact of Broadly Neutralizing Antibodies VRC01LS and 10-1074 on Maintenance of HIV Suppression in a Cohort of Early-Treated Children in Botswana (Dual bNAb Treatment in Children)

The purpose of this study is to evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children...

Peg-Interferon Alpha 2b Combined With Two Intravenous Broadly HIV-1 Neutralizing Antibodies 3BNC117 and 10-1074 (BEAT-2)

This study will evaluate the safety, tolerability and innate immune mechanisms activation following administration of the combination of Pegylated Interferon alpha 2b (peg-IFN-α2b) with t...

Vaccine Therapy in Preventing Cytomegalovirus in Healthy Participants

RATIONALE: Vaccines made from peptides may help the body build an immune response to kill cytomegalovirus. PURPOSE: This phase I trial is studying the side effects and best dose of vaccin...

Imaging the HIV Reservoir

Radiolabelling broadly neutralizing anti-HIV antibody 3BNC117 with a Copper-64 radio isotope for infusion into people with HIV followed by MRI/PET scanning to detect HIV in vivo.

Medical and Biotech [MESH] Definitions

Protein domains that are enriched in PROLINE. The cyclical nature of proline causes the peptide bonds it forms to have a limited degree of conformational mobility. Therefore the presence of multiple prolines in close proximity to each other can convey a distinct conformational arrangement to a peptide chain.

The GENETIC RECOMBINATION of the parts of two or more GENES resulting in a gene with different or additional regulatory regions, or a new chimeric gene product. ONCOGENE FUSION includes an ONCOGENE as at least one of the fusion partners and such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS. ARTIFICIAL GENE FUSION is carried out in vitro by RECOMBINANT DNA technology.

The GENETIC RECOMBINATION of the parts of two or more GENES, including an ONCOGENE as at least one of the fusion partners. Such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS.

The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.

Agents counteracting or neutralizing the action of POISONS.

Quick Search


DeepDyve research library

Relevant Topics

An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

Searches Linking to this Article