From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1sjt.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1sjt.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1sjt| PDB=1sjt | SCENE= }} | | {{STRUCTURE_1sjt| PDB=1sjt | SCENE= }} |
| | | | |
| - | '''MINI-PROINSULIN, TWO CHAIN INSULIN ANALOG MUTANT: DES B30, HIS(B 10)ASP, PRO(B 28)ASP, NMR, 20 STRUCTURES'''
| + | ===MINI-PROINSULIN, TWO CHAIN INSULIN ANALOG MUTANT: DES B30, HIS(B 10)ASP, PRO(B 28)ASP, NMR, 20 STRUCTURES=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Protein minimization highlights essential determinants of structure and function. Minimal models of proinsulin and insulin-like growth factor I contain homologous A and B domains as single-chain analogues. Such models (designated mini-proinsulin and mini-IGF-I) have attracted wide interest due to their native foldability but complete absence of biological activity. The crystal structure of mini-proinsulin, determined as a T3R3 hexamer, is similar to that of the native insulin hexamer. Here, we describe the solution structure of a monomeric mini-proinsulin under physiologic conditions and compare this structure to that of the corresponding two-chain analogue. The two proteins each contain substitutions in the B-chain (HisB10-->Asp and ProB28-->Asp) designed to destabilize self-association by electrostatic repulsion; the proteins differ by the presence or absence of a peptide bond between LysB29 and GlyA1. The structures are essentially identical, resembling in each case the T-state crystallographic protomer. Differences are observed near the site of cross-linking: the adjoining A1-A8 alpha-helix (variable among crystal structures) is less well-ordered in mini-proinsulin than in the two-chain variant. The single-chain analogue is not completely inactive: its affinity for the insulin receptor is 1500-fold lower than that of the two-chain analogue. Moreover, at saturating concentrations mini-proinsulin retains the ability to stimulate lipogenesis in adipocytes (native biological potency). These results suggest that a change in the conformation of insulin, as tethered by the B29-A1 peptide bond, optimizes affinity but is not integral to the mechanism of transmembrane signaling. Surprisingly, the tertiary structure of mini-proinsulin differs from that of mini-IGF-I (main-chain rms deviation 4.5 A) despite strict conservation of non-polar residues in their respective hydrophobic cores (side-chain rms deviation 4.9 A). Three-dimensional profile scores suggest that the two structures each provide acceptable templates for threading of insulin-like sequences. Mini-proinsulin and mini-IGF-I thus provide examples of homologous protein sequences encoding non-homologous structures.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9514738}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9514738 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_9514738}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| - | 1SJT is a [[Protein complex]] structure of sequences 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=1SJT OCA]. | + | 1SJT is a [[Protein complex]] structure of sequences 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=1SJT OCA]. |
| | | | |
| | ==Reference== | | ==Reference== |
| Line 35: |
Line 39: |
| | [[Category: Hormone]] | | [[Category: Hormone]] |
| | [[Category: Signal]] | | [[Category: Signal]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:47:37 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:45:19 2008'' |
Revision as of 13:45, 28 July 2008
Template:STRUCTURE 1sjt
MINI-PROINSULIN, TWO CHAIN INSULIN ANALOG MUTANT: DES B30, HIS(B 10)ASP, PRO(B 28)ASP, NMR, 20 STRUCTURES
Template:ABSTRACT PUBMED 9514738
About this Structure
1SJT is a Protein complex structure of sequences from Homo sapiens. Full experimental information is available from OCA.
Reference
Mini-proinsulin and mini-IGF-I: homologous protein sequences encoding non-homologous structures., Hua QX, Hu SQ, Jia W, Chu YC, Burke GT, Wang SH, Wang RY, Katsoyannis PG, Weiss MA, J Mol Biol. 1998 Mar 20;277(1):103-18. PMID:9514738
Page seeded by OCA on Mon Jul 28 16:45:19 2008
