The molecular mechanism of nuclear transport revealed by atomic-scale measurements
Abstract
Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 15, 2015
- Source ID
- 10.7554/elife.10027
Entities
People
- Alia Kamal
- David Cowburn
- Deniz B Temel
- Jaclyn Tetenbaum-novatt
- Kaushik Dutta
- Loren E Hough
- Michael P Rout
- Samuel Sparks
Organizations
- Albert Einstein College of Medicine
- Charles H. Revson Foundation
- Empire State Development Division of Science, Technology and Innovation
- National Institute of General Medical Sciences
- National Institutes of Health
- New York Structural Biology Center
- The Rockefeller University
- United States Department of Defense
- W. M. Keck Foundation