1g26

From Proteopedia

(Difference between revisions)

Revision as of 07:10, 24 March 2021

THE SOLUTION STRUCTURE OF A WELL-FOLDED PEPTIDE BASED ON THE 31-RESIDUE AMINO-TERMINAL SUBDOMAIN OF HUMAN GRANULIN A

Structural highlights

1g26 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1qgm, 1fwo
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[GRN_HUMAN] Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.^[1] ^[2] ^[3] Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:614706]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.^[4]

Function

[GRN_HUMAN] Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling. Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.

Publication Abstract from PubMed

Four amino acid substitutions were introduced into a peptide corresponding to the amino-terminal subdomain (30-31 residues) of human granulin A (HGA) in order to assess the contributions of a hydrophobic framework and other interactions to structure stabilization of the stack of two beta-hairpins. The resulting hybrid peptide, HGA 1-31 (D1V, K3H, S9I, Q20P) with four free cysteines, spontaneously formed a uniquely disulfide-bonded isomer with an expected [1-3, 2-4] disulfide pairing pattern. This peptide was characterized in detail by use of NMR and shown to assume a highly stable structure in solution, in contrast to the amino-terminal 1-30 fragment of human granulin A. The prototype peptide, or HGA 1-30 (C17S, C27S), had lower resistance to chemical reduction and proteolysis, broad NH and H(alpha) proton resonances, lower proton resonance dispersion, and no slowly exchanging amide protons. Two other peptides, HGA 1-30 (C17S, Q20P, C27S) and HGA 1-31 (D1V, K3H, S9I, C17S, C27S), with either Pro20 stabilizing a potential reverse turn or with a hydrophobic cluster consisting of Val1, His3, and Ile9, had sharper and slightly better dispersed NH and H(alpha) proton resonances, but still no slowly exchanging amide protons. The solution structure of HGA 1-31 (D1V, K3H, S9I, Q20P) indicates that it adopts a well-folded conformation of a stack of two beta-hairpins, as found for the amino-terminal subdomain of the prototypic carp granulin-1 with representative beta-hairpin stacks. These results highlight the importance of both hydrophobic and turn-stabilizing interactions for the structural integrity of the hairpin stack scaffold. The conformational stability appears to be maintained by a combination of the well-formed second beta-hairpin and two hydrophobic clusters, one located at the interface between the two beta-hairpins and the other on "top" of the first beta-hairpin. The implications of these findings for the design of conformationally stable hairpin stacks are discussed.

Design and solution structure of a well-folded stack of two beta-hairpins based on the amino-terminal fragment of human granulin A.,Tolkatchev D, Ng A, Vranken W, Ni F Biochemistry. 2000 Mar 21;39(11):2878-86. PMID:10715107^[5]

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

References

↑ Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006 Aug 24;442(7105):916-9. Epub 2006 Jul 16. PMID:16862116 doi:10.1038/nature05016
↑ Mukherjee O, Pastor P, Cairns NJ, Chakraverty S, Kauwe JS, Shears S, Behrens MI, Budde J, Hinrichs AL, Norton J, Levitch D, Taylor-Reinwald L, Gitcho M, Tu PH, Tenenholz Grinberg L, Liscic RM, Armendariz J, Morris JC, Goate AM. HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. Ann Neurol. 2006 Sep;60(3):314-22. PMID:16983685 doi:10.1002/ana.20963
↑ Mukherjee O, Wang J, Gitcho M, Chakraverty S, Taylor-Reinwald L, Shears S, Kauwe JS, Norton J, Levitch D, Bigio EH, Hatanpaa KJ, White CL, Morris JC, Cairns NJ, Goate A. Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Hum Mutat. 2008 Apr;29(4):512-21. PMID:18183624 doi:10.1002/humu.20681
↑ Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF, Sims KB, Lewis J, Lin WL, Dickson DW, Dahl HH, Bahlo M, Berkovic SF. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet. 2012 Jun 8;90(6):1102-7. doi: 10.1016/j.ajhg.2012.04.021. Epub, 2012 May 17. PMID:22608501 doi:10.1016/j.ajhg.2012.04.021
↑ Tolkatchev D, Ng A, Vranken W, Ni F. Design and solution structure of a well-folded stack of two beta-hairpins based on the amino-terminal fragment of human granulin A. Biochemistry. 2000 Mar 21;39(11):2878-86. PMID:10715107

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1g26"

@@ Line 3: / Line 3: @@
 <StructureSection load='1g26' size='340' side='right'caption='[[1g26]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1g26]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G26 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1g26]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G26 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qgm|1qgm]], [[1fwo|1fwo]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qgm|1qgm]], [[1fwo|1fwo]]</div></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=1g26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g26 OCA], [http://pdbe.org/1g26 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1g26 RCSB], [http://www.ebi.ac.uk/pdbsum/1g26 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1g26 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g26 OCA], [https://pdbe.org/1g26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g26 RCSB], [https://www.ebi.ac.uk/pdbsum/1g26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g26 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:[http://omim.org/entry/607485 607485]]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.<ref>PMID:16862116</ref> <ref>PMID:16983685</ref> <ref>PMID:18183624</ref>   Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:[http://omim.org/entry/614706 614706]]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.<ref>PMID:22608501</ref>
+[[https://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:[https://omim.org/entry/607485 607485]]; also known as tau-negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.<ref>PMID:16862116</ref> <ref>PMID:16983685</ref> <ref>PMID:18183624</ref>   Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:[https://omim.org/entry/614706 614706]]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.<ref>PMID:22608501</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.  Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
+[[https://www.uniprot.org/uniprot/GRN_HUMAN GRN_HUMAN]] Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.  Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

1g26

From Proteopedia

Revision as of 07:10, 24 March 2021

THE SOLUTION STRUCTURE OF A WELL-FOLDED PEPTIDE BASED ON THE 31-RESIDUE AMINO-TERMINAL SUBDOMAIN OF HUMAN GRANULIN A

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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