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Stress‐inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection
Author(s) -
Zanata Silvio M.,
Lopes Marilene H.,
Mercadante Adriana F.,
Hajj Glaucia N. M.,
Chiarini Luciana B.,
Nomizo Regina,
Freitas Adriana R. O.,
Cabral Ana L. B.,
Lee Kil S.,
Juliano Maria A.,
de Oliveira Elizabeth,
Jachieri Saul G.,
Burlingame Alma,
Huang Lan,
Linden Rafael,
Brentani Ricardo R.,
Martins Vilma R.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf325
Subject(s) - biology , immunoprecipitation , cytoplasm , plasma protein binding , gene isoform , blot , membrane protein , peptide sequence , microbiology and biotechnology , biochemistry , membrane , gene
Prions are composed of an isoform of a normal sialoglycoprotein called PrP c , whose physiological role has been under investigation, with focus on the screening for ligands. Our group described a membrane 66 kDa PrP c ‐binding protein with the aid of antibodies against a peptide deduced by complementary hydropathy. Using these antibodies in western blots from two‐dimensional protein gels followed by sequencing the specific spot, we have now identified the molecule as stress‐inducible protein 1 (STI1). We show that this protein is also found at the cell membrane besides the cytoplasm. Both proteins interact in a specific and high affinity manner with a K d of 10 −7 M. The interaction sites were mapped to amino acids 113–128 from PrP c and 230–245 from STI1. Cell surface binding and pull‐down experiments showed that recombinant PrP c binds to cellular STI1, and co‐immunoprecipitation assays strongly suggest that both proteins are associated in vivo . Moreover, PrP c interaction with either STI1 or with the peptide we found that represents the binding domain in STI1 induce neuropro tective signals that rescue cells from apoptosis.