Angela A. Garibaldi Week 7

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Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human anti-body

Introduction

  • HIV destroys CD4+ lymphocytes

Basic Structure

  • Viral envelope (responsible for entry of HIV to host cells)has glycoproteins which contain oligomeric spikes, trimeric spikes on the surface
    • gp41 (transmembrane envelope glycoprotein) anchors the spikes in the viral membrane
    • spike surface made of gp120 (exterior envelope glycoprotein) which have non-covalent interactions with each subunit of trimeric gp41 complex
  • 5 variable regions
    • 1-4 form loops exposed to the surface which are bonded at their bases by disulfide bonds.

Basic Entry and Binding

Structure

Structure determination

Structure of gp120

Figure 1

Figure 2

Interactions

CD4-gp120 interaction

Figure 3

Interfacial Cavities

Antibody interface

Figure 4

Oligomer and gp41 interactions

Conformational change in core gp120

Figure 5

Viral evasion of immune responses

Mechanistic implications for virus entry

Methods

Protein production, crystallization and data collection

Structure determination and refinement

Table 1

Structure Analysis

Definitions

  1. epitope -That part of an antigenic molecule to which the T-cell receptor responds; a site on a large molecule against which an antibody will be produced and to which it will bind. biology-online.org dictionary
  2. chemokine -
  3. oligomeric spike/complex -
  4. trimeric spike/complex -
  5. fusogenic -
  6. anti-hotspot -
  7. cavity -
  8. linchpin -
  9. humoral immune response -
  10. oligomeric occlusion -
  11. glycocalyx -