1sf1
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= INS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= INS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2hiu|2HIU]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sf1 OCA], [http://www.ebi.ac.uk/pdbsum/1sf1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sf1 RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Diabetes mellitus, rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], Hyperproinsulinemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: human insulin]] | [[Category: human insulin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:41:10 2008'' |
Revision as of 20:41, 30 March 2008
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| Gene: | INS (Homo sapiens) | ||||||
| Related: | 2HIU
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR STRUCTURE OF HUMAN INSULIN under Amyloidogenic Condition, 15 STRUCTURES
Contents |
Overview
Insulin undergoes aggregation-coupled misfolding to form a cross-beta assembly. Such fibrillation has long complicated its manufacture and use in the therapy of diabetes mellitus. Of interest as a model for disease-associated amyloids, insulin fibrillation is proposed to occur via partial unfolding of a monomeric intermediate. Here, we describe the solution structure of human insulin under amyloidogenic conditions (pH 2.4 and 60 degrees C). Use of an enhanced sensitivity cryogenic probe at high magnetic field avoids onset of fibrillation during spectral acquisition. A novel partial fold is observed in which the N-terminal segments of the A- and B-chains detach from the core. Unfolding of the N-terminal alpha-helix of the A-chain exposes a hydrophobic surface formed by native-like packing of the remaining alpha-helices. The C-terminal segment of the B-chain, although not well ordered, remains tethered to this partial helical core. We propose that detachment of N-terminal segments makes possible aberrant protein-protein interactions in an amyloidogenic nucleus. Non-cooperative unfolding of the N-terminal A-chain alpha-helix resembles that observed in models of proinsulin folding intermediates and foreshadows the extensive alpha --> beta transition characteristic of mature fibrils.
Disease
Known disease associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
About this Structure
1SF1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mechanism of insulin fibrillation: the structure of insulin under amyloidogenic conditions resembles a protein-folding intermediate., Hua QX, Weiss MA, J Biol Chem. 2004 May 14;279(20):21449-60. Epub 2004 Feb 26. PMID:14988398
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