The ankyrin repeat domain of Huntingtin interacting protein 14 contains a surface aromatic cage, a potential site for methyl-lysine binding

• Type of Material: Article
• Authors: Tiyu Gao, Emory University; Robert E. Collins, Emory University; John Horton, Emory University; Xing Zhang, Emory University; Rongguang Zhang, Argonne National Laboratory; Arunkumar Dhayalan, Jacobs University Bremen; Raluca Tamas, Jacobs University Bremen; Albert Jeltsch, Jacobs University Bremen; Xiaodong Cheng, Emory University
• Language: English
• Date: 2009-08-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Wiley-Liss, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/prot.22452/abstract;jsessionid=C0E3C6DC8E331994CBB25E3875A3E101.f03t01
• Title of Journal or Parent Work: Proteins
• ISSN: 0887-3585
• Volume: 76
• Issue: 3
• Start Page: 772
• End Page: 777
• Grant/Funding Information: National Institute of Health grants GM068680 and DK082678 supported this work.
• Keywords: epigenetics; ankyrin repeats; X-ray crystallography; Huntingtin interacting protein 14; methyl-lysine binding
• Research Categories: Chemistry, Biochemistry

Abstract

Huntingtin interacting protein 14 (HIP14), a membrane-bound palmitoyl transferase, palmitoylates a number of neuronal proteins (including Huntingtin) and affects the trafficking, stability, aggregation, and/or functional activity of substrate proteins. HIP14 contains an N-terminal ankyrin repeat domain that may function in its substrate recognition. Sequence analysis suggests that the HIP14 ankyrin repeats share approximately 50% identity with the ankyrin repeats of G9a and G9a-like protein (GLP) histone lysine methyltransferases. The crystal structure of the HIP14 ankyrin repeats reveals a surface aromatic cage, formed by two tryptophans, one tyrosine, and one methionine. The all-hydrophobic cage resembles the tri-methylated lysine binding pocket of the plant homeodomain (PHD) of human BPTF (bromodomain and PHD domain transcription factor).