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Cancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesis.
Lipper, Colin H; Paddock, Mark L; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel; Jennings, Patricia A.
Afiliação
  • Lipper CH; Departments of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, United States of America.
  • Paddock ML; Departments of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, United States of America.
  • Onuchic JN; Center for Theoretical Biological Physics and Department of Physics, Rice University, Houston, TX, 77005, United States of America.
  • Mittler R; Department of Biology, University of North Texas, Denton, TX, 76203, United States of America.
  • Nechushtai R; The Alexander Silberman Institute of Life Science, Hebrew University of Jerusalem, Edmond J. Safra Campus at Givat Ram, Jerusalem, 91904, Israel.
  • Jennings PA; Departments of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, United States of America.
PLoS One ; 10(10): e0139699, 2015.
Article em En | MEDLINE | ID: mdl-26448442
Iron-sulfur cluster biogenesis is executed by distinct protein assembly systems. Mammals have two systems, the mitochondrial Fe-S cluster assembly system (ISC) and the cytosolic assembly system (CIA), that are connected by an unknown mechanism. The human members of the NEET family of 2Fe-2S proteins, nutrient-deprivation autophagy factor-1 (NAF-1) and mitoNEET (mNT), are located at the interface between the mitochondria and the cytosol. These proteins have been implicated in cancer cell proliferation, and they can transfer their 2Fe-2S clusters to a standard apo-acceptor protein. Here we report the first physiological 2Fe-2S cluster acceptor for both NEET proteins as human Anamorsin (also known as cytokine induced apoptosis inhibitor-1; CIAPIN-1). Anamorsin is an electron transfer protein containing two iron-sulfur cluster-binding sites that is required for cytosolic Fe-S cluster assembly. We show, using UV-Vis spectroscopy, that both NAF-1 and mNT can transfer their 2Fe-2S clusters to apo-Anamorsin with second order rate constants similar to those of other known human 2Fe-2S transfer proteins. A direct protein-protein interaction of the NEET proteins with apo-Anamorsin was detected using biolayer interferometry. Furthermore, electrospray mass spectrometry of holo-Anamorsin prepared by cluster transfer shows that it receives both of its 2Fe-2S clusters from the NEETs. We propose that mNT and NAF-1 can provide parallel routes connecting the mitochondrial ISC system and the CIA. 2Fe-2S clusters assembled in the mitochondria are received by NEET proteins and when needed transferred to Anamorsin, activating the CIA.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Mitocondriais / Peptídeos e Proteínas de Sinalização Intracelular Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Mitocondriais / Peptídeos e Proteínas de Sinalização Intracelular Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos