Angela A. Garibaldi Week 7

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.

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 - 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
3. oligomeric spike/complex -
4. trimeric spike/complex -
5. fusogenic - Facilitating fusion of the viral envelope with the cellular plasma membrane. Nature Review Glossary
6. anti-hotspot -
7. 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
8. 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
9. humoral immune response - Those immune responses mediated by antibody. biology-online.org dictionary
10. oligomeric occlusion - 1. The act of closure or state of being closed. 2. The relationship between all of the components of the masticatory system in normal function, dysfunction and parafunction.3. Momentary complete closure of some area in the vocal tract, causing stoppage of the breath and accumulation of pressure. biology-online.org dictionary
11. glycocalyx - The region, seen by electron microscopy, external to the outer dense line of the plasma membranethat appears to be rich in glycosidic compounds such as proteoglycans and glycoproteins. Since these molecules are often integral membrane proteins and may be denatured by the processes of fixation for electron microscopy, it might be better to avoid the term or to refer to membrane glycoproteins or to proteoglycans associated with the cell surface. Dictionary of Cell and Molecular Biology
12. ectodomain- is the part of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and entry into cells during infection. Wikipedia