Intramolecular cohesion of coils mediated by phenylalanine--glycine motifs in the natively unfolded domain of a nucleoporin.
The nuclear pore complex (NPC) provides the sole aqueous conduit for macromolecular exchange between the nucleus and the cytoplasm of cells. Its diffusion conduit contains a size-selective gate formed by a family of NPC proteins that feature large, natively unfolded domains with phenylalanine-glycine repeats (FG domains). These domains of nucleoporins play key roles in establishing the NPC permeability barrier, but little is known about their dynamic structure. Here we used molecular modeling and biophysical techniques to characterize the dynamic ensemble of structures of a representative FG domain from the yeast nucleoporin Nup116. The results showed that its FG motifs function as intramolecular cohesion elements that impart order to the FG domain and compact its ensemble of structures into native premolten globular configurations. At the NPC, the FG motifs of nucleoporins may exert this cohesive effect intermolecularly as well as intramolecularly to form a malleable yet cohesive quaternary structure composed of highly flexible polypeptide chains. Dynamic shifts in the equilibrium or competition between intra- and intermolecular FG motif interactions could facilitate the rapid and reversible structural transitions at the NPC conduit needed to accommodate passing karyopherin-cargo complexes of various shapes and sizes while simultaneously maintaining a size-selective gate against protein diffusion.
Krishnan
V V
VV
Department of Applied Science, University of California Davis, Davis, California, United States of America.
Lau
Edmond Y
EY
Yamada
Justin
J
Denning
Daniel P
DP
Patel
Samir S
SS
Colvin
Michael E
ME
Rexach
Michael F
MF
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs / Q000502:physiology; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D008970:Molecular Weight; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D010649:Phenylalanine / Q000737:chemistry*; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D020836:Protein Structure, Quaternary; D020449:Repetitive Sequences, Amino Acid / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D013816:Thermodynamics
C077730:NUP116 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; D010649:Phenylalanine; D005998:Glycine