4hti

From Proteopedia

(Difference between revisions)

Revision as of 11:58, 18 March 2015

Crystallographic structure of the membrane-proximal ectodomain of the human receptor-type protein-tyrosine phosphatase phogrin

Structural highlights

4hti is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PTPRN2, KIAA0387 (HUMAN)
Activity:	Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PTPR2_HUMAN] Implicated in development of nervous system and pancreatic endocrine cells.^[1] ^[2]

Publication Abstract from PubMed

Phogrin/IA-2beta and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet beta-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and beta-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-A resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel beta-strands packed against two alpha-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.

X-ray structure of the mature ectodomain of phogrin.,Noguera ME, Primo ME, Jakoncic J, Poskus E, Solimena M, Ermacora MR J Struct Funct Genomics. 2015 Mar;16(1):1-9. doi: 10.1007/s10969-014-9191-0. Epub, 2014 Nov 26. PMID:25421040^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kawasaki E, Hutton JC, Eisenbarth GS. Molecular cloning and characterization of the human transmembrane protein tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes. Biochem Biophys Res Commun. 1996 Oct 14;227(2):440-7. PMID:8878534 doi:S0006-291X(96)91526-0
↑ Cui L, Yu WP, DeAizpurua HJ, Schmidli RS, Pallen CJ. Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in insulin-dependent diabetes. J Biol Chem. 1996 Oct 4;271(40):24817-23. PMID:8798755
↑ Noguera ME, Primo ME, Jakoncic J, Poskus E, Solimena M, Ermacora MR. X-ray structure of the mature ectodomain of phogrin. J Struct Funct Genomics. 2015 Mar;16(1):1-9. doi: 10.1007/s10969-014-9191-0. Epub, 2014 Nov 26. PMID:25421040 doi:http://dx.doi.org/10.1007/s10969-014-9191-0

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4hti"

@@ Line 2: / Line 2: @@
 <StructureSection load='4hti' size='340' side='right' caption='[[4hti]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4hti]] is a 1 chain structure with 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=4HTI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4hti]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTI FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPRN2, KIAA0387 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPRN2, KIAA0387 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hti OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hti RCSB], [http://www.ebi.ac.uk/pdbsum/4hti PDBsum]</span></td></tr>
@@ Line 11: / Line 11: @@
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-The receptor-type protein-tyrosine phosphatase (RPTP) phogrin is localized at the membrane of secretory granules of pancreatic islet beta-cells and, similarly to the closely related ICA512, plays a role in the regulation of insulin secretion, in ensuring proper granulogenesis and stability, and in the regulation of beta-cell growth. The mature membrane-proximal ectodomain of phogrin (MPE phogrin) was produced as a recombinant protein and characterized. CD, fluorescence, controlled proteolysis, size-exclusion chromatography, and multi-angle ligth scattering showed that it is a properly-folded monomeric domain. Equilibrium experiments, in the presence of guanidinium chloride and thermal unfolding, suggest a two-state mechanism with a DeltaG of 2.3-3.3 kcal/mol, respectively. The study establishes common features and differences of MPE phogrin and the homologous ectodomain of ICA512. A homology model of phogrin was built based in the x-ray structure of MPE ICA512. The model is a starting point for modeling the entire receptor and for testing the quaternary structure and interactions of this protein in vivo. A description of the membrane insertion mode and putative interacting surfaces of this large protein is fundamental for the understanding of its biological function.
+Phogrin/IA-2beta and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet beta-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and beta-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-A resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel beta-strands packed against two alpha-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.
-Biophysical Characterization of the Membrane-proximal Ectodomain of the Receptor-type Protein-tyrosine Phosphatase Phogrin.,Noguera ME, Primo ME, Sosa LN, Risso VA, Poskus E, Ermacora MR Protein Pept Lett. 2012 Sep 25. PMID:23016632<ref>PMID:23016632</ref>
+X-ray structure of the mature ectodomain of phogrin.,Noguera ME, Primo ME, Jakoncic J, Poskus E, Solimena M, Ermacora MR J Struct Funct Genomics. 2015 Mar;16(1):1-9. doi: 10.1007/s10969-014-9191-0. Epub, 2014 Nov 26. PMID:25421040<ref>PMID:25421040</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Protein-tyrosine-phosphatase]]
 [[Category: Ermacora, M R]]

4hti

From Proteopedia

Revision as of 11:58, 18 March 2015

Crystallographic structure of the membrane-proximal ectodomain of the human receptor-type protein-tyrosine phosphatase phogrin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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