# Atomic Structure of the Nuclear Pore Complex - Administrative Supplement

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $74,365

## Abstract

This equipment supplement does not modify the scope of the funded research but will facilitate
a parallel approach to realize the original aims in a timely manner. As such, the original abstract
is included.
Abstract
The enclosure of genetic information in the nucleus is one of the great hallmarks of evolution, but
creates the necessity for dedicated portals through which folded proteins and protein/nucleic acid
complexes can cross the nuclear envelope (NE). The nuclear pore complex (NPC), a cylindrical
supramolecular structure embedded in circular pores permeating the NE, is the sole gateway for
passage through the NE and can accomplish the selective bidirectional transport of macromolecules of
up to ~40 nm in diameter at a rate of several hundred events per second. Beyond its primary role in
nucleocytoplasmic transport, the NPC also contributes to additional modes of gene regulation for
example through direct interaction with the transcription and mRNA export machineries. The NPC thus
represents an essential organelle for all eukaryotic life and, accordingly, NPC dysfunction has been
associated with various forms of human disease. Architecturally, the NPC consists of a central
symmetric core to which asymmetric components called cytoplasmic filaments and nuclear basket are
attached. The NPC is built from ~34 different proteins termed nucleoporins that are each present in
multiple copies such that the entire assembly reaches the extraordinary mass of ~110 MDa in humans.
Nucleoporins are organized into distinct subcomplexes which constitute physiological building blocks of
the intact NPC in vivo. To determine the atomic architecture of the NPC, my group has been pursuing a
divide-and-conquer approach, in which we have mapped nucleoporin interactions, reconstituted
recombinant nucleoporin complexes and determined their crystal structures to be fit into cryo-electron
tomographic reconstructions of the intact NPC. In this way, we achieved a near-atomic composite
structure of the ~60MDa human NPC symmetric core in the previous grant period. Building on this
progress, we now propose to expand our structural characterization to still unresolved parts of the NPC
and to use our already gained knowledge to address fundamental NPC-associated cell biological
questions. Specifically, we plan to elucidate the molecular interactions in the NPC’s inner ring that are
essential for the formation of its central transport channel, and between the symmetric core and
transmembrane NPC components that are essential for NPC anchoring in the NE pores. The outcome
of the proposed research is expected to greatly increase our understanding of the molecular
mechanisms by which the NPC regulates nucleocytoplasmic transport and associated cellular
processes, while simultaneously creating a mechanistic basis for currently untreatable “nup diseases.”
Furthermore, the methodologies developed herein will serve as a paradigm for the characterization of
other essential cellular meg...

## Key facts

- **NIH application ID:** 10244832
- **Project number:** 3R01GM111461-06S1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Andre Hoelz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,365
- **Award type:** 3
- **Project period:** 2014-09-05 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244832

## Citation

> US National Institutes of Health, RePORTER application 10244832, Atomic Structure of the Nuclear Pore Complex - Administrative Supplement (3R01GM111461-06S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244832. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*