BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.
A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3057972?pdf=render |
| _version_ | 1828485689177538560 |
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| author | Akinori Hishiya Mortada Najem Salman Serena Carra Harm H Kampinga Shinichi Takayama |
| author_facet | Akinori Hishiya Mortada Najem Salman Serena Carra Harm H Kampinga Shinichi Takayama |
| author_sort | Akinori Hishiya |
| collection | DOAJ |
| description | A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy. |
| first_indexed | 2024-12-11T09:19:10Z |
| format | Article |
| id | doaj.art-e2813979c9364eeab68b89b71f2579b4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:19:10Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e2813979c9364eeab68b89b71f2579b42022-12-22T01:13:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1682810.1371/journal.pone.0016828BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.Akinori HishiyaMortada Najem SalmanSerena CarraHarm H KampingaShinichi TakayamaA homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy.http://europepmc.org/articles/PMC3057972?pdf=render |
| spellingShingle | Akinori Hishiya Mortada Najem Salman Serena Carra Harm H Kampinga Shinichi Takayama BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. PLoS ONE |
| title | BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. |
| title_full | BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. |
| title_fullStr | BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. |
| title_full_unstemmed | BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. |
| title_short | BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity. |
| title_sort | bag3 directly interacts with mutated alphab crystallin to suppress its aggregation and toxicity |
| url | http://europepmc.org/articles/PMC3057972?pdf=render |
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