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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Kim, Jeongho Lee, Kee Nyung Yi, Gwan-Su Yu, Myeong-Hee |
| Abstract | A thermostable mutation, F51L, at the hydrophobic core of human α1-antitrypsin (α1AT) increased the conformational stability of the molecule by decreasing the unfolding rate significantly without altering the refolding rate. The mutation specifically influenced the transition between the native state and a compact intermediate, which retained ∼70% of the far-UV CD signal, but which had most of the fluorescence signal already dequenched. The mutant α1AT protein was more resistant than the wild-type protein to the insertion of the tetradecapeptide mimicking the sequence of the reactive center loop, indicating that the mutation increases the closing of the central β-sheet, the A-sheet, in the native state. The F51L mutation enhanced the folding efficiency of the Z-type (E342K) genetic variation, which causes aggregation of the molecule in the liver. It has been shown previously that the aggregation of the Z protein occurs via loop-sheet polymerization, in which the reactive center loop of one molecule is inserted into the opening of the A-sheet of another molecule. Our results strongly suggest that the hydrophobic core of α1AT regulates the opening-closing of the A-sheet and that certain genetic variations that cause opening of the A-sheet can be corrected by inserting an additional stable mutation into the hydrophobic core. |
| Related Links | http://www.jbc.org/content/270/15/8597.abstract |
| Ending Page | 8601 |
| Starting Page | 8597 |
| Page Count | 5 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 15 |
| Volume Number | 270 |
| DOI | 10.1074/jbc.270.15.8597 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 1995-04-14 |
| Access Restriction | Open |
| Subject Keyword | Protein Chemistry and Structure |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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