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
- 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
- chemokine - class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c (chemokines, c), cc (chemokines, cc), and cxc (chemokines, cxc), according to variations in a shared cysteine motif. biology-online.org dictionary Small secreted proteins that stimulate chemotaxis of leucocytes. Chemokines can be subdivided into classes on the basis of conserved cysteine residues. The a -chemokines (IL-8, NAP-2, Gro- a , Gro- g , ENA-78 and GCP-2) have conserved C-X-C motif and are mainly chemotactic for neutrophils; the b -chemokines (MCP-1-5, MIP-1 a , MIP-1 b , eotaxin, RANTES) have adjacent cysteines (C-C) and attract monocytes, eosinophils or basophils; the g -chemokines have only one cysteine pair and are chemotactic for lymphocytes (lymphotactin), the d -chemokines are structurally rather different being membrane-anchored, have a C-X-X-X-C motif and are restricted (so far) to brain (neurotactin). Human genes for the a -chemokines are on Chr 4 and 10, for b -chemokines on Chr 17, for lymphotactin on Chr 1 and for neurotactin on Chr16. The receptors are G-protein coupled.Dictionary of Cell and Molecular Biology
- oligomeric spike/complex -
- trimeric spike/complex -
- fusogenic - Facilitating fusion of the viral envelope with the cellular plasma membrane. Nature Review Glossary
- anti-hotspot -
- cavity - a hollow place or space or a potential space, within the body or in one of its organs, it may be normal or pathological. biology-online.org dictionary
- linchpin - 1.A locking pin inserted in the end of a shaft, as in an axle, to prevent a wheel from slipping off. 2. A central cohesive element Farlex Dictionary
- humoral immune response - Those immune responses mediated by antibody. biology-online.org dictionary
- oligomeric occlusion -
- glycocalyx -
