“Prosaposin”的意思、由来-开放百科全书

This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator PrO[S]teINs.^[2] Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities.^[1]

Saposins A–D are required for the hydrolysis of certain sphingolipids by specific lysosomal hydrolases.^[3]

Family members

Structure

Every saposin contains about 80 amino acid residues and has six equally placed cysteines, two prolines, and a glycosylation site (two in saposin A, one each in saposins B, C, and D).^[3] Since saposins characteristics of extreme heat-stability, adundance of disulfide linkages, and resistance to most proteases, they are assumed to be extremely compact and rigidly disulfide-linked molecules. Each saposin has an α-helical structure that is seen as being important for stimulation because this structure is maximal at a pH of 4.5; which is optimal for many lysosomal hydrolases.^[3] This helical structure is seen in all (especially with the first region), but saposin has been predicted to have β-sheet configuration due to it first 24 amino acids of the N-end.^[5]

Function

They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes.^[10]^[11]

Clinical significance

Mutations in this gene have been associated with Gaucher disease, Tay–Sachs disease, and metachromatic leukodystrophy.^[2]

See also

References

1. ^¹{{cite web | title = Entrez Gene: PSAP prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5660| accessdate = }}
2. ^¹{{cite journal |vauthors=Morimoto S, Yamamoto Y, O'Brien JS, Kishimoto Y | title = Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseases | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 9 | pages = 3493–7 |date=May 1990 | pmid = 2110365 | pmc = 53927 | doi = 10.1073/pnas.87.9.3493| url = http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2110365 }}
3. ^¹²³{{cite journal |vauthors=Kishimoto Y, Hiraiwa M, O'Brien JS | title = Saposins: structure, function, distribution, and molecular genetics | journal = J. Lipid Res. | volume = 33 | issue = 9 | pages = 1255–67 |date=September 1992 | pmid = 1402395 | doi = | url = http://www.jlr.org/cgi/content/abstract/33/9/1255 }}
4. ^{{cite journal |vauthors=Morimoto S, Martin BM, Yamamoto Y, Kretz KA, O'Brien JS, Kishimoto Y | title = Saposin A: second cerebrosidase activator protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 9 | pages = 3389–93 |date=May 1989 | pmid = 2717620 | pmc = 287138 | doi = 10.1073/pnas.86.9.3389| url = http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2717620 }}
5. ^¹{{cite journal |vauthors=O'Brien JS, Kishimoto Y | title = Saposin proteins: structure, function, and role in human lysosomal storage disorders | journal = FASEB J. | volume = 5 | issue = 3 | pages = 301–8 |date=March 1991 | pmid = 2001789 | doi = | url = http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=2001789 }}
6. ^{{Citation |author=HUGO Gene Nomenclature Committee |authorlink=HUGO Gene Nomenclature Committee |title=GM2A |work=HGNC database |url=https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:4367 |accessdate=2016-03-13 |postscript=.}}
7. ^{{cite journal |vauthors=Ahn VE, Leyko P, Alattia JR, Chen L, Privé GG | title = Crystal structures of saposins A and C | journal = Protein Sci. | volume = 15 | issue = 8 | pages = 1849–57 |date=August 2006 | pmid = 16823039 | doi = 10.1110/ps.062256606 | url = | pmc = 2242594 }}
8. ^{{cite journal |vauthors=Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Privé GG | title = Crystal structure of saposin B reveals a dimeric shell for lipid binding | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 1 | pages = 38–43 |date=January 2003 | pmid = 12518053 | pmc = 140876 | doi = 10.1073/pnas.0136947100 | url = }}
9. ^¹{{cite journal |vauthors=Rossmann M, Schultz-Heienbrok R, Behlke J, Remmel N, Alings C, Sandhoff K, Saenger W, Maier T | title = Crystal structures of human saposins C and D: implications for lipid recognition and membrane interactions | journal = Structure | volume = 16 | issue = 5 | pages = 809–17 |date=May 2008 | pmid = 18462685 | doi = 10.1016/j.str.2008.02.016 | url = }}
10. ^{{cite journal |author=Ponting CP |title=Acid sphingomyelinase possesses a domain homologous to its activator proteins: saposins B and D |journal=Protein Sci. |volume=3 |issue=2 |pages=359–361 |year=1994 |pmid=8003971 |doi=10.1002/pro.5560030219 |pmc=2142785}}
11. ^{{cite journal|vauthors=Hofmann K, Tschopp J |title=Cytotoxic T cells: more weapons for new targets? |journal=Trends Microbiol. |volume=4 |issue=3 |pages=91–94|year=1996 |pmid=8868085 |doi=10.1016/0966-842X(96)81522-8}}