Long-Lived Folding Intermediates Predominate the Targeting-Competent Secretome (Structure)

Tsirigotaki et al. demonstrate that secretory mature domains inhabit a rich landscape of loosely packed folding intermediates essential for translocase recognition. Mature domains have elevated disorder and reduced hydrophobicity, and fold more slowly than cytoplasmic structural homologs. Some loose intermediates require signal peptides. Preproteins constitute a distinct protein class.