9OSC

Crystal structure of HP1gamma chromoshadow domain in complex with KAP1 peptide

Summary for 9OSC

• Entry DOI: 10.2210/pdb9osc/pdb
• Descriptor: Chromobox protein homolog 3, Transcription intermediary factor 1-beta (3 entities in total)
• Functional Keywords: hp1, csd domain, kap1, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 8937.31

Authors

Selvam, K.,Liu, J.,Singh, R.K.,Gaurav, N.,Kutateladze, T.G. (deposition date: 2025-05-23, release date: 2026-02-04)

Primary citation

Gaurav, N.,Qin, W.,Selvam, K.,Zhou, Z.,Liu, J.,Yin, Y.,Singh, R.K.,O'Hara, R.A.,Tavaf, Z.,Kumar, A.,Kono, H.,Narlikar, G.J.,Banaszynski, L.A.,Leonhardt, H.,Kutateladze, T.G.
HP1 gamma self-assembles and cooperates with KAP1 in repression of long noncoding RNA AI662270 in ESCs.
Cell Rep, 45:116874-116874, 2026

PubMed Abstract: HP1s are involved in the assembly of heterochromatin and transcriptional regulation. Here, we report the molecular mechanisms underlying binding of the chromoshadow domain of HP1γ (HP1γ) to the transcriptional co-repressor KAP1 and HP1γ self-assembly. Using crystallography, NMR, and mass photometry, we show that HP1γ recognizes the HP1 box of KAP1 (KAP1) and forms a relatively stable dimer of dimers, assembled in an antiparallel manner, in contrast to the corresponding HP1α complex, which shows concentration-dependent oligomerization and arrangement of HP1α protomers in a parallel manner. The β-sheet interface between HP1γ dimers is stabilized through electrostatic interactions, unlike the hydrophobic β-sheet interface of HP1α. In vivo rescue experiments using KAP1- and HP1-knockout mouse embryonic stem cells reveal a unique cooperative action of KAP1 and HP1γ, but not other HP1s, in the repression of the long noncoding RNA AI662270, underscoring the notion that cellular functions of HP1 proteins are not redundant.

PubMed: 41575850
DOI: 10.1016/j.celrep.2025.116874

Experimental method

X-RAY DIFFRACTION (1.77 Å)