Single-stranded nucleic acids promote SAMHD1 complex formation

SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi–Goutieres syndrome (AGS), an inflammatory encephalopathy that mimics...

Descripción completa

Detalles Bibliográficos
Autores principales:	Tüngler, Victoria, Staroske, Wolfgang, Kind, Barbara, Dobrick, Manuela, Kretschmer, Stefanie, Schmidt, Franziska, Krug, Claudia, Lorenz, Mike, Chara, Osvaldo, Schwille, Petra, Lee-Kirsch, Min Ae
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2013
Materias:	Ciencias Exactas Medicina SAMHD1 Aicardi–Goutières syndrome Fluorescence cross-correlation spectroscopy Nucleic acids
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/139718
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-139718
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Ciencias Exactas Medicina SAMHD1 Aicardi–Goutières syndrome Fluorescence cross-correlation spectroscopy Nucleic acids
spellingShingle	Ciencias Exactas Medicina SAMHD1 Aicardi–Goutières syndrome Fluorescence cross-correlation spectroscopy Nucleic acids Tüngler, Victoria Staroske, Wolfgang Kind, Barbara Dobrick, Manuela Kretschmer, Stefanie Schmidt, Franziska Krug, Claudia Lorenz, Mike Chara, Osvaldo Schwille, Petra Lee-Kirsch, Min Ae Single-stranded nucleic acids promote SAMHD1 complex formation
topic_facet	Ciencias Exactas Medicina SAMHD1 Aicardi–Goutières syndrome Fluorescence cross-correlation spectroscopy Nucleic acids
description	SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi–Goutieres syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.
format	Articulo Articulo
author	Tüngler, Victoria Staroske, Wolfgang Kind, Barbara Dobrick, Manuela Kretschmer, Stefanie Schmidt, Franziska Krug, Claudia Lorenz, Mike Chara, Osvaldo Schwille, Petra Lee-Kirsch, Min Ae
author_facet	Tüngler, Victoria Staroske, Wolfgang Kind, Barbara Dobrick, Manuela Kretschmer, Stefanie Schmidt, Franziska Krug, Claudia Lorenz, Mike Chara, Osvaldo Schwille, Petra Lee-Kirsch, Min Ae
author_sort	Tüngler, Victoria
title	Single-stranded nucleic acids promote SAMHD1 complex formation
title_short	Single-stranded nucleic acids promote SAMHD1 complex formation
title_full	Single-stranded nucleic acids promote SAMHD1 complex formation
title_fullStr	Single-stranded nucleic acids promote SAMHD1 complex formation
title_full_unstemmed	Single-stranded nucleic acids promote SAMHD1 complex formation
title_sort	single-stranded nucleic acids promote samhd1 complex formation
publishDate	2013
url	http://sedici.unlp.edu.ar/handle/10915/139718
work_keys_str_mv	AT tunglervictoria singlestrandednucleicacidspromotesamhd1complexformation AT staroskewolfgang singlestrandednucleicacidspromotesamhd1complexformation AT kindbarbara singlestrandednucleicacidspromotesamhd1complexformation AT dobrickmanuela singlestrandednucleicacidspromotesamhd1complexformation AT kretschmerstefanie singlestrandednucleicacidspromotesamhd1complexformation AT schmidtfranziska singlestrandednucleicacidspromotesamhd1complexformation AT krugclaudia singlestrandednucleicacidspromotesamhd1complexformation AT lorenzmike singlestrandednucleicacidspromotesamhd1complexformation AT charaosvaldo singlestrandednucleicacidspromotesamhd1complexformation AT schwillepetra singlestrandednucleicacidspromotesamhd1complexformation AT leekirschminae singlestrandednucleicacidspromotesamhd1complexformation
bdutipo_str	Repositorios
_version_	1764820458373382145

Single-stranded nucleic acids promote SAMHD1 complex formation

Ejemplares similares