1m12

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[[Image:1m12.gif|left|200px]]
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{{STRUCTURE_1m12| PDB=1m12 | SCENE= }}
{{STRUCTURE_1m12| PDB=1m12 | SCENE= }}
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'''NMR solution structure of human Saposin C'''
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===NMR solution structure of human Saposin C===
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==Overview==
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Saposin C binds to membranes to activate lipid degradation in lysosomes. To get insights into saposin C's function, we have determined its three-dimensional structure by NMR and investigated its interaction with phospholipid vesicles. Saposin C adopts the saposin-fold common to other members of the family. In contrast, the electrostatic surface revealed by the NMR structure is remarkably different. We suggest that charge distribution in the protein surface can modulate membrane interaction leading to the functional diversity of this family. We find that the binding of saposin C to phospholipid vesicles is a pH-controlled reversible process. The pH dependence of this interaction is sigmoidal, with an apparent pK(a) for binding close to 5.3. The pK(a) values of many solvent-exposed Glu residues are anomalously high and close to the binding pK(a). Our NMR data are consistent with the absence of a conformational change prior to membrane binding. All this information suggests that the negatively charged electrostatic surface of saposin C needs to be partially neutralized to trigger membrane binding. We have studied the membrane-binding behavior of a mutant of saposin C designed to decrease the negative charge of the electrostatic surface. The results support our conclusion on the importance of protein surface neutralization in binding. Since saposin C is a lysosomal protein and pH gradients occur in lysosomes, we propose that lipid degradation in the lysosome could be switched on and off by saposin C's reversible binding to membranes.
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{{ABSTRACT_PUBMED_14674747}}
==About this Structure==
==About this Structure==
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1M12 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M12 OCA].
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1M12 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M12 OCA].
==Reference==
==Reference==
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[[Category: Alpha-helice]]
[[Category: Alpha-helice]]
[[Category: Disulfide bridge]]
[[Category: Disulfide bridge]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:30:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 22:58:55 2008''

Revision as of 19:58, 2 July 2008

Template:STRUCTURE 1m12

NMR solution structure of human Saposin C

Template:ABSTRACT PUBMED 14674747

About this Structure

1M12 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Solution structure of human saposin C: pH-dependent interaction with phospholipid vesicles., de Alba E, Weiler S, Tjandra N, Biochemistry. 2003 Dec 23;42(50):14729-40. PMID:14674747

Page seeded by OCA on Wed Jul 2 22:58:55 2008

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