Related Experiment Video

Updated: Jun 6, 2026

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
07:10

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay

Published on: September 14, 2014

Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody

Michael M Freeman1, Michael S Seaman, Sophia Rits-Volloch

  • 1Division of Molecular Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, 3 Blackfan Circle, Boston, MA 02115, USA.

Structure (London, England : 1993)
|December 8, 2010
PubMed

Insights

Ibalizumab, an anti-CD4 antibody, effectively blocks HIV-1 infection by binding to CD4 without disrupting essential immune functions. Its structure reveals it grips CD4 without needing to crosslink, offering insights into HIV entry inhibition.

Area of Science:

  • Structural Biology
  • Immunology
  • Virology

Background:

  • Ibalizumab is a humanized monoclonal antibody targeting CD4.
  • It inhibits HIV-1 infection by binding to a specific CD4 epitope.
  • This binding avoids interference with CD4 interactions crucial for immune functions.

Purpose of the Study:

  • To determine the crystal structure of the ibalizumab Fab fragment in complex with CD4 domains D1-D2.
  • To elucidate the binding mechanism of ibalizumab to CD4.
  • To understand how ibalizumab inhibits HIV-1 entry at a molecular level.

Main Methods:

  • X-ray crystallography was used to obtain the structure at 2.2 Å resolution.
  • Analysis of the ibalizumab-CD4 complex structure.
  • Functional assays to assess viral blocking activity of different ibalizumab forms.

Main Results:

  • The crystal structure reveals ibalizumab binds to the BC-loop of CD4 domain D2.
  • This binding site is distinct from gp120 and MHC-II binding sites.
  • Ibalizumab effectively blocks viral infection in both monovalent and bivalent forms, indicating crosslinking is not required.
  • CD4 exhibits minimal conformational changes upon ibalizumab binding, and its structural rigidity is not essential for inhibition.

Conclusions:

  • Ibalizumab's unique binding mode to CD4 provides a structural basis for its potent HIV-1 inhibition.
  • The findings suggest that CD4 crosslinking is unnecessary for ibalizumab's antiviral activity.
  • This structural understanding can inform the design of novel CD4-based immunogens and therapies for HIV-1 entry.

More Related Videos

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging07:29

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Published on: December 1, 2011

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding10:50

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

Published on: September 15, 2010

Related Concept Videos

Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...