| Autor: |
P S, Brzovic, J E, Meza, M C, King, R E, Klevit |
| Rok vydání: |
2001 |
| Předmět: |
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| Zdroj: |
The Journal of biological chemistry. 276(44) |
| ISSN: |
0021-9258 |
| Popis: |
Cancer-predisposing missense mutations in the RING domain of BRCA1 primarily target Zn(2+)-liganding residues. Here we report on the structural consequences of such mutations introduced into the second Zn(2+) site (Site II) of the BRCA1 RING domain and their effect on the interaction with the BARD1 RING domain. Each of the BRCA1 Site II mutants still interact and form a stable heterodimer with BARD1. Limited proteolysis of BRCA1/BARD1 complexes, monitored by matrix-assisted laser desorption ionization time-of-flight spectrometry, show that the mutations cause a local structural perturbation that is primarily confined to the second Zn(2+) binding loop of the BRCA1 subunit. These findings are consistent with the structure of the BRCA1/BARD1 heterodimer, which shows this region is well removed from the helices required for dimerization with BARD1. Instead, the mutations alter a region of BRCA1 that appears to be required for interaction with ubiquitin-conjugating enzymes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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