2RO1

NMR Solution Structures of Human KAP1 PHD finger-bromodomain

Summary for 2RO1

• Entry DOI: 10.2210/pdb2ro1/pdb
• Descriptor: Transcription intermediary factor 1-beta, ZINC ION (2 entities in total)
• Functional Keywords: kap, tif, phd finger, bromodomain, sumo, acetylation, alternative splicing, metal-binding, nucleus, phosphoprotein, repressor, transcription, transcription regulation, zinc, zinc-finger
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: Q13263
• Total number of polymer chains: 1
• Total formula weight: 21173.77

Authors

Zeng, L.,Yap, K.L.,Ivanov, A.V.,Wang, X.,Mujtaba, S.,Plotnikova, O.,Rauscher, F.J. (deposition date: 2008-03-04, release date: 2008-05-20, Last modification date: 2024-05-29)

Primary citation

Zeng, L.,Yap, K.L.,Ivanov, A.V.,Wang, X.,Mujtaba, S.,Plotnikova, O.,Rauscher, F.J.,Zhou, M.M.
Structural insights into human KAP1 PHD finger-bromodomain and its role in gene silencing
Nat.Struct.Mol.Biol., 15:626-633, 2008

PubMed Abstract: The tandem PHD finger-bromodomain, found in many chromatin-associated proteins, has an important role in gene silencing by the human co-repressor KRAB-associated protein 1 (KAP1). Here we report the three-dimensional solution structure of the tandem PHD finger-bromodomain of KAP1. The structure reveals a distinct scaffold unifying the two protein modules, in which the first helix, alpha(Z), of an atypical bromodomain forms the central hydrophobic core that anchors the other three helices of the bromodomain on one side and the zinc binding PHD finger on the other. A comprehensive mutation-based structure-function analysis correlating transcriptional repression, ubiquitin-conjugating enzyme 9 (UBC9) binding and SUMOylation shows that the PHD finger and the bromodomain of KAP1 cooperate as one functional unit to facilitate lysine SUMOylation, which is required for KAP1 co-repressor activity in gene silencing. These results demonstrate a previously unknown unified function for the tandem PHD finger-bromodomain as an intramolecular small ubiquitin-like modifier (SUMO) E3 ligase for transcriptional silencing.

PubMed: 18488044
DOI: 10.1038/nsmb.1416

Experimental method

SOLUTION NMR