The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family
Open accessAbstract
Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.
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Self-citationStructural basis of PROTAC cooperative recognition for selective protein degradation
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Metadata
- Authors
- Filippakopoulos, P., Picaud, S., Mangos, M., Keates, T., Lambert, J.-P., Barsyte-Lovejoy, D., Felletar, I., Volkmer, R., Müller, S., Pawson, T., Gingras, A.-C., Arrowsmith, C. H., & Knapp, S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 149
- Issue
- 1
- Pages
- 214-231
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2123647733
- Cited by
- 1,694
- References
- 15
- FWCI
- 35.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Filippakopoulos, P., Picaud, S., Mangos, M., Keates, T., Lambert, J.-P., Barsyte-Lovejoy, D., Felletar, I., Volkmer, R., Müller, S., Pawson, T., Gingras, A.-C., Arrowsmith, C. H., & Knapp, S. (2012). Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family. Cell. https://doi.org/10.1016/j.cell.2012.02.013
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