Lecture 4: Nuclear Envelope Part 1

NPC Core Structural Modules, Periphery Structures, and Central Channel

Core Structural Module

1. Core scaffold: Inner and outer ring complexes, inner ring sandwiched by two outer rings (cytoplasmic and nucleoplasmic)

2. Linker Nucleoporins: Links the rings together; anchors FG Nups to the core scaffold

3. Membrane ring: Direct contact with the membrane and core scaffold AND anchors NPC to pore membrane; composed of 3-4 transmembrane Nups

Periphery Structures

1. Cytoplasmic filaments: initial capture of cargo/ternary complex; docking site for ranGAP for hydrolysis

2. Nuclear Basket: formed by 8 protein filaments that emanate from the core scaffold, protrude into the nucleoplasm → sometimes converge into a distal ring

Central Channel (FG Nups)

1. 1/3 of all Nups are present along the NPC length

2. Gel-like meshwork of FG Nucleoporins

3. Selective limit >40 kDa

Importin-β Passing Through the NPC

1. Structural Basis: Interaction between importin-beta (solenoid structure) and channel FG repeats

2. Interaction Dynamics: Transient, weak, multivalent interaction (rapid binding/unbinding like monkey bars)

3. Speed: Millisecond-fast transport despite non-linear (back and forth trajectory), but it gets through

NPC Basket in Transcription and mRNA processing

1. Association with the euchromatin at the nuclear basket

2. Recruits chromatin modifiers (unwinding heterochromatin), transcription factors, and RNA polymerase

3. Pre-mRNA processing: association of splicing machinery

4. RNA Export: Recruits export factors (TREX2)

5. Associates with active gene expression

DISCARD

DISCARD