Neutralization Properties of Anti-interferon Monoclonal Antibody Sifalimumab Flashcards
What is molecular replacement?
a known molecular model to solve the unknown crystal structure of a related molecule. MR enables the solution of the crystallographic phase problem by providing initial estimates of the phases of the new structure from a previously known structure
What is the role of cytokines in the immune system?
cytokines play a very important role, both directly (for example, blocking viral replication by the interferons) and by means of different immune-modulatory mechanisms that trigger the inflammatory response, produce and elevation on the body temperature, activate NK cells and macrophages, etc
what are cytokines?
category of small proteins (~5–20 kDa) that are important in cell signaling.
Give some cells that produce cytokines
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell.
what does interferon-α/β receptor bind?
type I interferons including interferon-α and -β.
describe the interferon-α/β receptor
heteromeric cell surface receptor composed of one chain with two subunits
what signalling pathway does the interferon-α/β receptor activate when bound to type 1 interferons?
The JAK-STAT signaling pathway (transmits information from extracellular chemical signals to the nucleus resulting in DNA transcription and expression of genes involved in immunity, proliferation, differentiation, apoptosis and oncogenesis)
What is systemic lupus erythematosus?
an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body
What are the symptoms of lupus erythematosus?
Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission when there are few symptoms
What is Sjogren’s syndrome?
In Sjogren’s syndrome, the mucous membranes and moisture-secreting glands of your eyes and mouth are usually affected first — resulting in decreased production of tears and saliva
What does analytical grade of chemicals mean?
a chemical compound of a known high standard of purity.
What are complementarity determining regions?
part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antigen
What do a set of complentarity determining regions constitute?
a paratope
What is PyMOL?
Python-enhanced molecular graphics tool
- a molecular visualization system
describe vapor diffusion
the most commonly employed method of protein crystallization. In this method, a droplet containing purified protein, buffer, and precipitant are allowed to equilibrate with a larger reservoir containing similar buffers and precipitants in higher concentrations. Initially, the droplet of protein solution contains comparatively low precipitant and protein concentrations, but as the drop and reservoir equilibrate, the precipitant and protein concentrations increase in the drop. If the appropriate crystallization solutions are used for a given protein, crystal growth will occur in the drop
why is vapor diffusion used over other crystallization techniques?
because it allows for gentle and gradual changes in concentration of protein and precipitant concentration, which aid in the growth of large and well-ordered crystals
draw an annotated diagram of hanging drop vapor diffusion
see net
Why were the first 14 amino acids of both IFN-a2A molecules in the asymmetric unit built last?
because of the larger conformational differences.
What does the TLS Motion Determination program do?
analyzes a macromolecular crystal structure for evidence of flexibility.
What is amine coupling?
one of the most common methods to immobilize a protein or a small molecule containing primary
amine group through a covalent bond on biosensors used in QCM (Quartz
Crystal Microbalance),
What is r.m.s deviation?
The root-mean-square deviation (RMSD) or root-mean-square error (RMSE) is a frequently used measure of the differences between values (sample and population values) predicted by a model or an estimator and the values actually observed.
what is coordinate error value?
Disorder in a crystal is reflected in lower resolution of the diffraction data,. Disorder in the coordinates based on that data can be modeled by introducing B-factors for each atom. They model atomic positions being displaced (by an average distance that is related to the B-factor) from an average position (given by the coordinates).
what are
homodimers?
a protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues
what are orthorhombic crystals?
In crystallography, the orthorhombic crystal system is one of the 7 crystal systems. Orthorhombic lattices result from stretching a cubic lattice along two of its orthogonal pairs by two different factors, resulting in a rectangular prism with a rectangular base (a by b) and height (c), such that a, b, and c are distinct.
What are interferons?
a group of signaling proteins made and released by host cells in response to the presence of several pathogens
What are the 3 families in the 4-helical superfamily?
Long-chain cytokines
Short-chain cytokines
Interferons
What causes a gender bias in immunopathology in women?
a mutually positive regulatory feedback loop between type I IFNs and estrogen receptor-α… thus resulting in an increased production of type I IFNs and associated immunopathology in women
