NDLI: Identification of Binding Sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L

Content Provider	PubMed Central
Author	Sanders, Shaun S. Mui, Katherine K. N. Sutton, Liza M. Hayden, Michael R.
Editor	Ariga, Hiroyoshi
Copyright Year	2014
Abstract	Huntington disease is an adult onset neurodegenerative disease characterized by motor, cognitive, and psychiatric dysfunction, caused by a CAG expansion in the HTT gene. Huntingtin Interacting Protein 14 (HIP14) and Huntingtin Interacting Protein 14-like (HIP14L) are palmitoyl acyltransferases (PATs), enzymes that mediate the post-translational addition of long chain fatty acids to proteins in a process called palmitoylation. HIP14 and HIP14L interact with and palmitoylate HTT and are unique among PATs as they are the only two that have an ankyrin repeat domain, which mediates the interaction between HIP14 and HTT. These enzymes show reduced interaction with and palmitoylation of mutant HTT, leading to increased mutant HTT inclusion formation and toxicity. The interaction between HIP14 and HTT goes beyond that of only an enzyme–substrate interaction as HTT is essential for the full enzymatic activity of HIP14. It is important to further understand and characterize the interactions of HTT with HIP14 and HIP14L to guide future efforts to target and enhance this interaction and increase enzyme activity to remediate palmitoylation of HTT and their substrates, as well as to understand the relationship between the three proteins. HIP14 and HIP14L have been previously shown to interact with HTT amino acids 1–548. Here the interaction of HIP14 and HIP14L with N- and C-terminal HTT 1–548 deletion mutations was assessed. We show that HTT amino acids 1–548 were sufficient for full interaction of HTT with HIP14 and HIP14L, but partial interaction was also possible with HTT 1–427 and HTT 224–548. To further characterize the binding domain we assessed the interaction of HIP14-GFP and HIP14L-GFP with 15Q HTT 1-548Δ257-315. Both enzymes showed reduced but not abolished interaction with 15Q HTT 1-548Δ257-315. This suggests that two potential binding domains exist, one around residues 224 and the other around 427, for the PAT enzymes HIP14 and HIP14L.
Related Links	http://dx.doi.org/10.1371/journal.pone.0090669
Starting Page	90669
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Huntingtin-interacting Proteins, HIP14 and HIP14L, Mediate Dual Functions, Palmitoyl Acyltransferase and Mg2+ Transport* S⃞

Dysregulated Striatal Neuronal Processing and Impaired Motor Behavior in Mice Lacking Huntingtin Interacting Protein 14 (HIP14)

Huntingtin-interacting Proteins, HIP14 and HIP14L, Mediate Dual Functions, Palmitoyl Acyltransferase and Mg2+ Transport

Identification of Ligand Binding Sites of Proteins Using the Gaussian Network Model

Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

Modeling the Quantitative Specificity of DNA-Binding Proteins from Example Binding Sites

Quantification Assays for Total and Polyglutamine-Expanded Huntingtin Proteins

Binding Sites Analyser (BiSA): Software for Genomic Binding Sites Archiving and Overlap Analysis

Prediction of Metal Ion–Binding Sites in Proteins Using the Fragment Transformation Method

Identification of Binding Sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L

Similar Documents

Huntingtin-interacting Proteins, HIP14 and HIP14L, Mediate Dual Functions, Palmitoyl Acyltransferase and Mg2+ Transport* S⃞

Dysregulated Striatal Neuronal Processing and Impaired Motor Behavior in Mice Lacking Huntingtin Interacting Protein 14 (HIP14)

Huntingtin-interacting Proteins, HIP14 and HIP14L, Mediate Dual Functions, Palmitoyl Acyltransferase and Mg2+ Transport

Identification of Ligand Binding Sites of Proteins Using the Gaussian Network Model

Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

Modeling the Quantitative Specificity of DNA-Binding Proteins from Example Binding Sites

Quantification Assays for Total and Polyglutamine-Expanded Huntingtin Proteins

Binding Sites Analyser (BiSA): Software for Genomic Binding Sites Archiving and Overlap Analysis

Prediction of Metal Ion–Binding Sites in Proteins Using the Fragment Transformation Method

Identification of Binding Sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L