Biology Flashcards
the bio that I need to know for my field
Nanobody
Nanobody, AKA single-domain antibody (sdAb), is an antibody fragment consisting of the recombinant variable domain of an antibody heavy chain. Nanobodies are antibody-derived therapeutic proteins with the structure and functional properties of naturally occurring heavy-chain antibodies.
Periplasm and periplasmic expression
A concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the gram-negative bacterial outer membrane. Sometimes, proteins are expressed in the periplasm in E. coli, rather than in the cytoplasm. This can help with proper protein folding, easier purification, applying PTMs, and incorporating secretion signals. Periplasmic expression is not always used; sometimes cytoplasmic expression is better.
Ramachandran plot
A way to visualize energetically allowed regions for backbone dihedral angles ψ (torsion angle of N-Calpha bond) against φ (torsion angle of Calpha-C bond) of amino acid residues in protein structure. These bonds are relatively free to rotate. Ramachandran used computer models of small polypeptides to systematically vary these values, aiming to find stable conformations, and examined each structure for close contacts between atoms. If atoms come closer than the sum of their Van per Waals radii, there is a steric clash (except for Glycine). Red on the plot = no steric clashes (alpha=helix and beta-sheet conformations). Yellow = allowed regions if slightly shorter vdc radii are used in the calculation, allowing atoms to come a bit closer together; this brings out a region corresponding to left-handed alpha-helix.
Van der Waals radius
The van der Waals radius of an atom is the radius of an imaginary hard sphere representing the distance of closest approach for another atom. It’s intrinsically approximate because atoms in molecules are not spherical.
Ig-like fold (IGF)
One of the most prevalent folds in nature, an essential building block of antibodies and receptors. IGFs consist of two stacked beta-sheets. They tend to engage in non-local interactions. Their edge B-strands cause susceptibility to aggregation.
Beta-Barrel
A fold present in both soluble and membrane proteome, with applications as small molecule binders, transporters, and sensors. Consists of 8 antiparallel B-strands with precise hydrogen bonding patterns. Other features like glycine kinks, B-bulges, and tryptophan corners can alleviate backbone strain and allow for continuous hydrogen bond connectivity.
Glycine kinks
Structural motifs that alleviate backbone strain in beta-barrels
TIM-barrel
An extremely important protein topology which supports enzymatic active sites. Attractive candidate (but long-standing challenge!!) for protein engineering, as novel TIM-barrels could promote novel catalytic functions in enzymes. TIM-barrels are comprised of 8 parallel-paired B-strands, each separated by an alpha helix resulting in long-range interactions between the B-strands.
Claudin fold
Claudins are a class of proteins involved in the formation of tight junctions, critical for controlling the flow of molecules between layers of epithelial and endothelial cells. Claudin folds consist of an alpha/beta mixed secondary structure where there are 4 transmembrane alpha helices and an extracellular B-sheet. The composition of the B-sheet determines the type of tight junction, resulting in high selective permeability.
- therapeutic relevance: claudin-targeting therapies hold great promise for cancer, and soluble claudin analogues could introduce a novel route to screen for Claudin binders
Rhomboid Protease Fold (RPF)
An intricate membrane topology consisting of six transmembrane alpha helical domains, many intricate loops and long-range contacts. It harbors a serine-histidine catalytic dyad buried in the cell membrane, allowing it to cleave transmembrane protein domains, which plays an important role in cell signaling.
GPCR fold
one of the most prevalent membrane folds in nature. the core topology consists of 7 transmembrane helices that facilitate numerous non-local interactions, allowing them to bind a variety of ligands including photoreceptors, odors, pheromones, hormones, and neurotransmitters
GPCRs
the largest and most diverse family of membrane receptors in eukaryotes, playing important roles in signaling pathways. About 34% of all FDA-approved drugs target GPCRs
Bio-layer interferometry (BLI)
optical biosensing technology that analyzes biomolecular interactions in real-time without the need for fluorescent labeling. relies on phase shift-wavelength correlation created between interference patterns off of two unique surfaces on the tip of a biosensor. applications in quantifying binding strength, measuring protein interactions, and identifying properties of reaction kinetics, such as rate constants and reaction rates.
