Peroxisomes, membrane protein

The ratio of peaks for peptides derived from 42 high abundance yeast proteins was examined for the wild type versus cln2 mutant strains (Oda et al., 1999). Only two of the proteins, a peroxisomal membrane protein and S-adenosylmethionine synthase 2, exhibited significant differences in expression between the strains. The biological significance of this observation is not yet known but the study does indicate that changes of >20% in expression levels can be detected using the technique (Oda et al., 1999). 

Adrenoleukodystrophy X-linked Peroxisomal membrane protein in the ABC transporter family Decreased peroxidation of saturated, very-long-chain fatty acids, causing their accumulation in brain, adrenals and other tissues variable phenotypes with regard to hypomyelination see text 1,26, Ch. 40... 

Owing to the small number of known peroxisomal membrane proteins, the signals (mPTSs) that direct them to the membrane are not well characterized. In one example, mPTS is found in the fourth loop (20 residues) of a 6 membrane-spanning protein. The loop faces to the matrix side. In another example, mPTS was found in the N-terminal 40-residue segment on the matrix side. Both of them contain a 5-residue stretch rich in basic amino acids and seem to be a part of the mPTS. 

Surprisingly, it turned out that some of peroxisomal membrane proteins are synthesized at the ER, cotranslationally. This seems a unique example that breaks the independence between the free ribosome system and the membrane-bound ribosome system (another example is found in a sorting mechanism into the vacuole). This phenomenon may be interpreted that the peroxisome may originate from the endoplasmic reticulum, evolutionally. 

The gene for X-ALD encodes a peroxisomal membrane protein whose function is required for VLCFA oxidation, so VLCFAs accumulate in tissues and spill over into plasma and urine. 

Both the integral membrane proteins of peroxisomes as well as the peroxisomal matrix proteins are synthesised on free polyribosomes and are specifically targeted to peroxisomes via dedicated peroxisomal targeting signals. The biogenesis of peroxisomes follows a sequential pattern, which involves first the insertion of peroxisomal membrane proteins into the membrane of the pre-peroxisomal structure, derived from the endoplasmic reticulum, followed by insertion of the various matrix proteins. 

Bartles JR, Khoun S, Lin X, et al. 1990. Peroxisome proliferator-induced alterations in the expression and modification of rat hepatocyte plasma membrane proteins. Cancer Res 506 669-676. 

Ferguson, G.P., Datta, A., Baumgartner, J., Roop, R.M., II, Carlson, R.W., Walker, G.C. Similarity to peroxisomal-membrane protein family reveals that Sinorhizobium and Brucella BacA affect lipid-A fatty acids. Proc Natl Acad Sci USA 101 (2004) 5012-5017. 

For many years, it was assumed that the inability of patients with X-ALD to degrade VLCFA was due to a primary deficiency of the first enzyme in this pathway, very long chain fatty acyl-CoA (VLCF-CoA) synthase. Indeed, studies in cultured skin fibroblasts from patients with X-ALD have revealed that this enzyme activity is decreased when compared to cells from normal controls. However, when the X-ALD gene was isolated in 1993, it was discovered that the underlying defect is the deficiency of a peroxisomal membrane protein, called ALD... 

Finally, peroxisomes contain another unique machinery for protein import and membrane protein assembly. 

Honsho, M., and Fujiki, Y (2001). Topogenesis of peroxisomal membrane protein requires a short, positively charged intervening-loop sequence and flanking hydrophobic segments—study using human membrane protein PMP34. /. Biol. Chem. 276, 9375-9382. 

In the human genetic disease X-linked adreno-leukodystrophy (ADL), peroxisomal oxidation of very long chain fatty acids is defective. The ADL gene encodes the peroxisomal membrane protein that trans-... 

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