1pw3
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1pw3.gif|left|200px]] | + | [[Image:1pw3.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure of JtoR68S''' | + | {{Structure |
| + | |PDB= 1pw3 |SIZE=350|CAPTION= <scene name='initialview01'>1pw3</scene>, resolution 1.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CD:CADMIUM ION'>CD</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= Jto ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of JtoR68S''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1PW3 is a [ | + | 1PW3 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=1PW3 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vlambda6 proteins., Wall JS, Gupta V, Wilkerson M, Schell M, Loris R, Adams P, Solomon A, Stevens F, Dealwis C, J Mol Recognit. 2004 Jul-Aug;17(4):323-31. PMID:[http:// | + | Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vlambda6 proteins., Wall JS, Gupta V, Wilkerson M, Schell M, Loris R, Adams P, Solomon A, Stevens F, Dealwis C, J Mol Recognit. 2004 Jul-Aug;17(4):323-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15227639 15227639] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 20: | Line 29: | ||
[[Category: light chain]] | [[Category: light chain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:29:41 2008'' |
Revision as of 11:29, 20 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | Jto (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of JtoR68S
Overview
Primary (AL) amyloidosis results from the pathologic deposition of monoclonal light chains as amyloid fibrils. Studies of recombinant-derived variable region (VL) fragments of these proteins have shown an inverse relationship between thermodynamic stability and fibrillogenic potential. Further, ionic interactions within the VL domain were predicted to influence the kinetics of light chain fibrillogenicity, as evidenced from our analyses of a relatively stable Vlambda6 protein (Jto) with a long range electrostatic interaction between Asp and Arg side chains at position 29 and 68, respectively, and an unstable, highly fibrillogenic Vlambda6 protein (Wil) that had neutral amino acids at these locations. To test this hypothesis, we have generated two Jto-related mutants designed to disrupt the interaction between Asp 29 and Arg 68 (JtoD29A and JtoR68S). Although the thermodynamic stabilities of unfolding for these two molecules were identical, they exhibited very different kinetics of fibril formation: the rate of JtoD29A fibrillogenesis was slow and comparable to the parent molecule, whereas that of JtoR68S was significantly faster. High-resolution X-ray diffraction analyses of crystals prepared from the two mutants having the same space group and unit cell dimensions revealed no significant main-chain conformational changes. However, several notable side-chain alterations were observed in JtoR68S, as compared with JtoD29A, that resulted in the solvent exposure of a greater hydrophobic surface and modifications in the electrostatic potential surface. We posit that these differences contributed to the enhanced fibrillogenic potential of the Arg 68 mutant, since both Jto mutants lacked the intrachain ionic interaction and were equivalently unstable. The information gleaned from our studies has provided insight into structural parameters that in addition to overall thermodynamic stability, contribute to the fibril forming propensity of immunoglobulin light chains.
About this Structure
1PW3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vlambda6 proteins., Wall JS, Gupta V, Wilkerson M, Schell M, Loris R, Adams P, Solomon A, Stevens F, Dealwis C, J Mol Recognit. 2004 Jul-Aug;17(4):323-31. PMID:15227639
Page seeded by OCA on Thu Mar 20 13:29:41 2008
