2g4e: Difference between revisions

Revision as of 20:42, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2g4e.png

Template:STRUCTURE 2g4e

Crystal structure of transthyretin mutant I84A at neutral pHCrystal structure of transthyretin mutant I84A at neutral pH

Template:ABSTRACT PUBMED 17196219

About this StructureAbout this Structure

2G4E is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin., Pasquato N, Berni R, Folli C, Alfieri B, Cendron L, Zanotti G, J Mol Biol. 2007 Feb 23;366(3):711-9. Epub 2006 Dec 1. PMID:17196219

A comparative analysis of 23 structures of the amyloidogenic protein transthyretin., Hornberg A, Eneqvist T, Olofsson A, Lundgren E, Sauer-Eriksson AE, J Mol Biol. 2000 Sep 22;302(3):649-69. PMID:10986125

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OCA

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 {{STRUCTURE_2g4e|  PDB=2g4e  |  SCENE=  }}
-'''Crystal structure of transthyretin mutant I84A at neutral pH'''
+===Crystal structure of transthyretin mutant I84A at neutral pH===
-==Overview==
+<!--
-Several proteins, including transthyretin (TTR), can generate in tissues extracellular insoluble aggregates, in the form of fibrils, that are associated with pathological states known as amyloidoses. To date, more than 80 different TTR point mutations have been associated with hereditary amyloidosis in humans. In vitro, the formation of amyloid fibrils by human TTR is known to be triggered by acidic pH. We show here that, in vitro, the natural amyloidogenic I84S and the non-natural I84A TTR mutant forms exhibit a propensity to produce fibrils in an acidic medium significantly higher than that of wild-type TTR. The two mutant forms have been crystallized at both neutral and acidic pH. Their neutral pH crystal structures are very similar to that of wild-type TTR, consistent with previous evidence indicating that only minor structural changes are induced by amyloidogenic mutations. On the contrary, their crystal structures at moderately low pH (4.6) show significant conformational differences as compared to their neutral pH structures. Remarkably, such changes are not induced in wild-type TTR crystallized at low pH. The most relevant consist of the unwinding of the TTR short alpha-helix and of the change in conformation of the loop connecting the alpha-helix to beta-strand F. Only one monomer of the crystallographic dimer is affected, causing a disruption of the tetrameric symmetry. This asymmetry and a possible destabilization of the tetrameric quaternary structure of TTR may be responsible for the amyloidogenic potential of the two TTR mutant forms at low pH.
+The line below this paragraph, {{ABSTRACT_PUBMED_17196219}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17196219 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_17196219}}
 ==About this Structure==
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 ==Reference==
 Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin., Pasquato N, Berni R, Folli C, Alfieri B, Cendron L, Zanotti G, J Mol Biol. 2007 Feb 23;366(3):711-9. Epub 2006 Dec 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17196219 17196219]
+A comparative analysis of 23 structures of the amyloidogenic protein transthyretin., Hornberg A, Eneqvist T, Olofsson A, Lundgren E, Sauer-Eriksson AE, J Mol Biol. 2000 Sep 22;302(3):649-69. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10986125 10986125]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
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 [[Category: Point mutation]]
 [[Category: Ttr]]
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