4x1l
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | ==Profilin | + | ==Structural basis for mutation-induced destabilization of Profilin 1 in ALS== |
<StructureSection load='4x1l' size='340' side='right' caption='[[4x1l]], [[Resolution|resolution]] 2.16Å' scene=''> | <StructureSection load='4x1l' size='340' side='right' caption='[[4x1l]], [[Resolution|resolution]] 2.16Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| Line 11: | Line 11: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.<ref>PMID:18573880</ref> | [[http://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.<ref>PMID:18573880</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the destabilized M114T variant. In contrast, the E117G mutation only modestly perturbs the structure and stability of PFN1, an observation that reconciles the occurrence of this mutation in the control population. These findings suggest that a destabilized form of PFN1 underlies PFN1-mediated ALS pathogenesis. | ||
| + | |||
| + | Structural basis for mutation-induced destabilization of profilin 1 in ALS.,Boopathy S, Silvas TV, Tischbein M, Jansen S, Shandilya SM, Zitzewitz JA, Landers JE, Goode BL, Schiffer CA, Bosco DA Proc Natl Acad Sci U S A. 2015 Jun 8. pii: 201424108. PMID:26056300<ref>PMID:26056300</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 12:11, 1 July 2015
Structural basis for mutation-induced destabilization of Profilin 1 in ALS
| |||||||||||
