In the US,

50 million without health insurance

250 million with health insurance

Bafilomycin

a proton pump inhibitor, prevents acidification of late endosome and lysosome

Using caprylic acid

In mildly acidic conditions, the addition of short-chain fatty acids such as caprylic acid to serum will precipitate most serum proteins with the exception of the IgG molecules.

Ammnonium Sulfate Precipitation

removes proteins frrom solition. Proteins in solution form hydrogen bonds with water through their exposed polar and ionic groups. When high concentrations of samll, highly charged ions such as ammonium or sulfate are added, these groups compete with the proteins for binding to water. This removes the water molecules from the protein and decrease its solubility, resulting in precipitation. This can be reversed convieniently by lowering the concentration of ammonium sulfate.

What is a geranylgeranyl group?

prenylation, farnesylation....?

A protein isofom is a version of a protein with only small differences to another isoform of the same protein. Different forms of a protein may be produced from different but related genes or may arise from the same gene by alterenative splicing. A large number of isoforms are caused by single nucleotide polymorphisms, small genetic differences between alleles of the same gene.

The Rab GTPase family

Rab GTPases belong to the Ras superfamily and central regulators of vesicle budding, motility, docking and fusion. Rab proteins swich between GTP-bound and GDP-bound forms. The GTP-bound form is an active state, and the GDP-bound form is an inactive state.

There are many members; human have approximately 70 Rab GTPases, S. cerevisiae (11), C.elegans(29), D. melanogastor(26), P.falciparum(11).

In general, Rab GTPase differ most in their carboxil termini, which has been implicated in subcellular targeting, whereas regions involved in guanine-nucleotide binding are most conserved.

Within cells, they are localized to the cytosolic face of distinct intracellular membranes. Their reversible membrane localization depends on the post-translational modification of a cystein motif at the very carboxyl terminus (CXXX, CC, CXC, CCXX or CCXXX where X is any amino acid), with one or two highly hydrophobic geranylgeranyl groups.

A Rab escrot protein (REP) presents rabprotein to the geranylgeranyl transferase. REP can functions as a chaperone that keeps the hydrophobic, geranylgeranylated Rab soluble and delivers it to the appropriate membrane.

The Rab GTPase cycle

The Rab GTPase switches between GDP- and GTP- bound forms.

Conversion from GDP to GTP-bound form caused by nucleotide exchange, catalyzed by a GDP/GTP exchange factor(GEF).

Conversion from the GTP- and GDP-bound form occurs by GTP hydrolysis, facilitated by a GTPase-activating protein(GAP).

The GTP-bound form interacts with effector molecules, whereas the GDP-bound form interacts with Rab escort protein(REP) and GDP dissociation inhibitor(GDI).

Dissociation of Rab-GDI coomplex is catalyzed by a GDI-displacement factor, which enables transfer of Rabs from GDI to membranes.

オバケの英語のスキット(母音編）とLost in Translation