2H8N

Structure of a glutamine-rich domain from histone deacetylase 4

Summary for 2H8N

• Entry DOI: 10.2210/pdb2h8n/pdb
• Descriptor: Histone deacetylase 4 (1 entity in total)
• Functional Keywords: alpha helix, polar zipper, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P56524
• Total number of polymer chains: 4
• Total formula weight: 54613.39

Authors

Guo, L.,Han, A.,Bates, D.L.,Chen, L. (deposition date: 2006-06-07, release date: 2007-02-27, Last modification date: 2024-02-14)

Primary citation

Guo, L.,Han, A.,Bates, D.L.,Cao, J.,Chen, L.
Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains.
Proc.Natl.Acad.Sci.Usa, 104:4297-4302, 2007

PubMed Abstract: Glutamine-rich sequences exist in a wide range of proteins across multiple species. A subset of glutamine-rich sequences has been shown to form amyloid fibers implicated in human diseases. The physiological functions of these sequence motifs are not well understood, partly because of the lack of structural information. Here we have determined a high-resolution structure of a glutamine-rich domain from human histone deacetylase 4 (HDAC4) by x-ray crystallography. The glutamine-rich domain of HDAC4 (19 glutamines of 68 residues) folds into a straight alpha-helix that assembles as a tetramer. In contrast to most coiled coil proteins, the HDAC4 tetramer lacks regularly arranged apolar residues and an extended hydrophobic core. Instead, the protein interfaces consist of multiple hydrophobic patches interspersed with polar interaction networks, wherein clusters of glutamines engage in extensive intra- and interhelical interactions. In solution, the HDAC4 tetramer undergoes rapid equilibrium with monomer and intermediate species. Structure-guided mutations that expand or disrupt hydrophobic patches drive the equilibrium toward the tetramer or monomer, respectively. We propose that a general role of glutamine-rich motifs be to mediate protein-protein interactions characteristic of a large component of polar interaction networks that may facilitate reversible assembly and disassembly of protein complexes.

PubMed: 17360518
DOI: 10.1073/pnas.0608041104

Experimental method

X-RAY DIFFRACTION (2.6 Å)