Long Unfolded Linkers Facilitate Membrane Protein Import Through the Nuclear Pore Complex

• Published in: Science (American Association for the Advancement of Science) 2011-07, Vol.333 (6038), p.90-93
• Main Authors: Meinema, Anne C., Laba, Justyna K., Hapsari, Rizqiya A., Otten, Renee, Mulder, Frans A. A., Kralt, Annemarie, van den Bogaart, Geert, Lusk, C. Patrick, Poolman, Bert, Veenhoff, Liesbeth M.
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Binding; Biological and medical sciences; Endoplasmic Reticulum - metabolism; Fluorescence; Freight; Fundamental and applied biological sciences. Psychology; Imports; Karyopherins - chemistry; Karyopherins - metabolism; Localization; Membrane proteins; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Microscopy; Models, Biological; Molecular and cellular biology; Molecular Sequence Data; Nuclear Envelope - metabolism; Nuclear Localization Signals; Nuclear membrane; Nuclear pore; Nuclear Pore - metabolism; Nuclear Pore Complex Proteins - chemistry; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Porosity; Protein Folding; Protein Structure, Tertiary; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Scaffolds; Transport
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1205741

Active nuclear import of soluble cargo involves transport factors that shuttle cargo through the nuclear pore complex (NPC) by binding to phenylalanine-glycine (FG) domains. How nuclear membrane proteins cross through the NPC to reach the inner membrane is presently unclear. We found that at least a 120-residue-long intrinsically disordered linker was required for the import of membrane proteins carrying a nuclear localization signal for the transport factor karyopherin-α. We propose an import mechanism for membrane proteins in which an unfolded linker slices through the NPC scaffold to enable binding between the transport factor and the FG domains in the center of the NPC.