Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumo...

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Autores principales:	Srinivasa R Penumutchu, Ruey-Hwang Chou, Chin Yu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00a0a6dba27c4cb4b8e8f0cab063d07b
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spelling	oai:doaj.org-article:00a0a6dba27c4cb4b8e8f0cab063d07b2021-11-25T06:06:15ZStructural insights into calcium-bound S100P and the V domain of the RAGE complex.1932-620310.1371/journal.pone.0103947https://doaj.org/article/00a0a6dba27c4cb4b8e8f0cab063d07b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25084534/?tool=EBIhttps://doaj.org/toc/1932-6203The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+)-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC), fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2)-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM). NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.Srinivasa R PenumutchuRuey-Hwang ChouChin YuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103947 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Srinivasa R Penumutchu Ruey-Hwang Chou Chin Yu Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
description	The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+)-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC), fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2)-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM). NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.
format	article
author	Srinivasa R Penumutchu Ruey-Hwang Chou Chin Yu
author_facet	Srinivasa R Penumutchu Ruey-Hwang Chou Chin Yu
author_sort	Srinivasa R Penumutchu
title	Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
title_short	Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
title_full	Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
title_fullStr	Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
title_full_unstemmed	Structural insights into calcium-bound S100P and the V domain of the RAGE complex.
title_sort	structural insights into calcium-bound s100p and the v domain of the rage complex.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/00a0a6dba27c4cb4b8e8f0cab063d07b
work_keys_str_mv	AT srinivasarpenumutchu structuralinsightsintocalciumbounds100pandthevdomainoftheragecomplex AT rueyhwangchou structuralinsightsintocalciumbounds100pandthevdomainoftheragecomplex AT chinyu structuralinsightsintocalciumbounds100pandthevdomainoftheragecomplex
_version_	1718414142842339328

Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

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