2r0o
From Proteopedia
(New page: 200px<br /><applet load="2r0o" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r0o" /> ''''''<br /> ==About this Structure== is a [h...) |
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[[Image:2r0o.jpg|left|200px]]<br /><applet load="2r0o" size="350" color="white" frame="true" align="right" spinBox="true" | [[Image:2r0o.jpg|left|200px]]<br /><applet load="2r0o" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2r0o" /> | + | caption="2r0o, resolution 2.20Å" /> |
| - | ''''''<br /> | + | '''Crystal structure of the actin-binding domain of human alpha-actinin-4 mutant(K255E)'''<br /> |
| + | |||
| + | ==Overview== | ||
| + | Mutations in alpha-actinin-4 have been linked to familial focal segmental, glomerulosclerosis (FSGS), a common renal disorder in humans, and produce, an apparent increase in the actin-binding affinity of alpha-actinin-4 in, vitro. One of the mutations, in particular, Lys255Glu, falls in the middle, of the actin-binding interface of the actin-binding domain (ABD). The ABD, consists of tandem calponin homology (CH) domains (CH1 and CH2). The, crystal structures of most ABDs display a compact conformation, characterized by extensive inter-CH interactions. However, the, conformation of F-actin-bound ABDs is unsettled. Some electron microscopy, studies find that the compact conformation is preserved upon binding to, F-actin, whereas other studies suggest that the CHs separate and the ABD, becomes extended. The Lys255Glu mutation in CH2 is significant in this, regard since it removes a crucial inter-CH interaction with Trp147 of CH1, thought to stabilize the compact conformation. Together, the increased, actin-binding affinity and the removal of this important inter-CH contact, suggested that the Lys255Glu mutation might facilitate the transition, toward the open ABD conformation proposed by some of the electron, microscopy studies. However, the crystal structure of the ABD of, alpha-actinin-4 Lys255Glu mutant described here displays the canonical, compact conformation. Furthermore, the sedimentation coefficients by, analytical ultracentrifugation of wild-type and FSGS mutant ABDs, (Lys255Glu, Ser262Pro, and Thr259Ile) are nearly identical (2.50+/-0.03 S), and are in good agreement with the theoretical value calculated from the, crystal structure (2.382 S), implying that the compact conformation is, retained in solution. The absence of a structural change suggests that the, compact ABD conformation observed in the majority of the structures is, highly stable and is preserved in solution, even in FSGS mutant ABDs. | ||
==About this Structure== | ==About this Structure== | ||
| - | + | 2R0O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Gol+Binding+Site+For+Residue+A+1'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Residue+B+2'>AC2</scene> and <scene name='pdbsite=AC3:Gol+Binding+Site+For+Residue+B+3'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R0O OCA]. | |
| - | [[Category: | + | |
| + | ==Reference== | ||
| + | Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis., Lee SH, Weins A, Hayes DB, Pollak MR, Dominguez R, J Mol Biol. 2008 Feb 15;376(2):317-24. Epub 2007 Dec 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18164029 18164029] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Single protein]] | ||
| + | [[Category: Dominguez, R.]] | ||
| + | [[Category: Lee, S.H.]] | ||
| + | [[Category: GOL]] | ||
| + | [[Category: actin-binding protein]] | ||
| + | [[Category: actin-crosslinking]] | ||
| + | [[Category: calcium]] | ||
| + | [[Category: calponin homology domain]] | ||
| + | [[Category: ch domain]] | ||
| + | [[Category: cytoplasm]] | ||
| + | [[Category: disease mutation]] | ||
| + | [[Category: glomeruloscleros spectrin family]] | ||
| + | [[Category: nucleus]] | ||
| + | [[Category: phosphorylation]] | ||
| + | [[Category: structural protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 17:23:46 2008'' |
Revision as of 15:23, 6 February 2008
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Crystal structure of the actin-binding domain of human alpha-actinin-4 mutant(K255E)
Overview
Mutations in alpha-actinin-4 have been linked to familial focal segmental, glomerulosclerosis (FSGS), a common renal disorder in humans, and produce, an apparent increase in the actin-binding affinity of alpha-actinin-4 in, vitro. One of the mutations, in particular, Lys255Glu, falls in the middle, of the actin-binding interface of the actin-binding domain (ABD). The ABD, consists of tandem calponin homology (CH) domains (CH1 and CH2). The, crystal structures of most ABDs display a compact conformation, characterized by extensive inter-CH interactions. However, the, conformation of F-actin-bound ABDs is unsettled. Some electron microscopy, studies find that the compact conformation is preserved upon binding to, F-actin, whereas other studies suggest that the CHs separate and the ABD, becomes extended. The Lys255Glu mutation in CH2 is significant in this, regard since it removes a crucial inter-CH interaction with Trp147 of CH1, thought to stabilize the compact conformation. Together, the increased, actin-binding affinity and the removal of this important inter-CH contact, suggested that the Lys255Glu mutation might facilitate the transition, toward the open ABD conformation proposed by some of the electron, microscopy studies. However, the crystal structure of the ABD of, alpha-actinin-4 Lys255Glu mutant described here displays the canonical, compact conformation. Furthermore, the sedimentation coefficients by, analytical ultracentrifugation of wild-type and FSGS mutant ABDs, (Lys255Glu, Ser262Pro, and Thr259Ile) are nearly identical (2.50+/-0.03 S), and are in good agreement with the theoretical value calculated from the, crystal structure (2.382 S), implying that the compact conformation is, retained in solution. The absence of a structural change suggests that the, compact ABD conformation observed in the majority of the structures is, highly stable and is preserved in solution, even in FSGS mutant ABDs.
About this Structure
2R0O is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
Reference
Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis., Lee SH, Weins A, Hayes DB, Pollak MR, Dominguez R, J Mol Biol. 2008 Feb 15;376(2):317-24. Epub 2007 Dec 4. PMID:18164029
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