2MH0

Solution NMR structure of the p300 Taz2:ETAD1 complex

Summary for 2MH0

• Entry DOI: 10.2210/pdb2mh0/pdb
• NMR Information: BMRB: 19610
• Descriptor: Transcription factor E2-alpha, Histone acetyltransferase p300 (2 entities in total)
• Functional Keywords: transcription-transferase complex, transcription/transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P15923; Cytoplasm: Q09472
• Total number of polymer chains: 2
• Total formula weight: 14375.84

Authors

Langelaan, D.N.,Smith, S.P.,Chitayat, S. (deposition date: 2013-11-12, release date: 2014-11-12, Last modification date: 2024-05-15)

Primary citation

Lochhead, M.R.,Brown, A.D.,Kirlin, A.C.,Chitayat, S.,Munro, K.,Findlay, J.E.,Baillie, G.S.,LeBrun, D.P.,Langelaan, D.N.,Smith, S.P.
Structural insights into TAZ2 domain-mediated CBP/p300 recruitment by transactivation domain 1 of the lymphopoietic transcription factor E2A.
J.Biol.Chem., 295:4303-4315, 2020

PubMed Abstract: The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding protein P300 (p300). This interaction is necessary for B-cell maturation and oncogenesis by E2A-PBX1 and occurs through conserved ΦΦΦ motifs (with Φ denoting a hydrophobic amino acid) in AD1 and AD2. However, disruption of this interaction via mutation of the KIX domain in CBP/p300 does not completely abrogate binding of E2A and E2A-PBX1. Here, we determined that E2A-AD1 and E2A-AD2 also interact with the TAZ2 domain of CBP/p300. Characterization of the TAZ2:E2A-AD1(1-37) complex indicated that E2A-AD1 adopts an α-helical structure and uses its ΦΦΦ motif to bind TAZ2. Whereas this region overlapped with the KIX recognition region, key KIX-interacting E2A-AD1 residues were exposed, suggesting that E2A-AD1 could simultaneously bind both the KIX and TAZ2 domains. However, we did not detect a ternary complex involving E2A-AD1, KIX, and TAZ2 and found that E2A containing both intact AD1 and AD2 is required to bind to CBP/p300. Our findings highlight the structural plasticity and promiscuity of E2A-AD1 and suggest that E2A binds both the TAZ2 and KIX domains of CBP/p300 through AD1 and AD2.

PubMed: 32098872
DOI: 10.1074/jbc.RA119.011078

Experimental method

SOLUTION NMR