6L87

Solution structure of the tandem PWWP-ARID domains of human RBBP1

Summary for 6L87

• Entry DOI: 10.2210/pdb6l87/pdb
• Descriptor: AT-rich interactive domain-containing protein 4A (1 entity in total)
• Functional Keywords: dna binding, pwwp, arid, gene regulation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 26604.19

Authors

Gong, W.B.,Perrett, S.,Feng, Y.G. (deposition date: 2019-11-05, release date: 2021-01-06, Last modification date: 2024-05-15)

Primary citation

Gong, W.,Liang, Q.,Tong, Y.,Perrett, S.,Feng, Y.
Structural insight into chromatin recognition by multiple domains of the tumor suppressor RBBP1.
J.Mol.Biol., :167224-167224, 2021

PubMed Abstract: Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin.

PubMed: 34506790
DOI: 10.1016/j.jmb.2021.167224

Experimental method

SOLUTION NMR