title: NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum.
abstract: Nascent polypeptide-associated complex (NAC) was initially found to bind to any segment of the nascent chain except signal sequences. In this way, NAC is believed to prevent mistargeting due to binding of signal recognition particle (SRP) to signalless ribosome nascent chain complexes (RNCs). Here we revisit the interplay between NAC and SRP. NAC does not affect SRP function with respect to signalless RNCs; however, NAC does affect SRP function with respect to RNCs targeted to the endoplasmic reticulum (ER). First, early recruitment of SRP to RNCs containing a signal sequence within the ribosomal tunnel is NAC dependent. Second, NAC is able to directly and tightly bind to nascent signal sequences. Third, SRP initially displaces NAC from RNCs; however, when the signal sequence emerges further, trimeric NAC·RNC·SRP complexes form. Fourth, upon docking to the ER membrane NAC remains bound to RNCs, allowing NAC to shield cytosolically exposed nascent chain domains not only before but also during cotranslational translocation. The combined data indicate a functional interplay between NAC and SRP on ER-targeted RNCs, which is based on the ability of the two complexes to bind simultaneously to distinct segments of a single nascent chain.
authors: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, University of Freiburg, Freiburg, Germany.
authors: Ying
authors: Y
authors: Zhang
authors: Uta
authors: U
authors: Berndt
authors: Hanna
authors: H
authors: Gölz
authors: Arlette
authors: A
authors: Tais
authors: Stefan
authors: S
authors: Oellerer
authors: Tina
authors: T
authors: Wölfle
authors: Edith
authors: E
authors: Fitzke
authors: Sabine
authors: S
authors: Rospert
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D012269:Ribosomal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D018271:Signal Recognition Particle / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C078340:EGD1 protein, S cerevisiae; D018832:Molecular Chaperones; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle; D014157:Transcription Factors; C096099:nascent-polypeptide-associated complex; C041672:ribosomal protein L34; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II