Neurofibromin

Introduction

Structure

Domains

GRD domain

SEC-PH

CSRD and CTD

Important Structural Features

Active Site

Arginine Finger

Conformations

RAS Complex

Mechanism of Ras Coupled with Neurofibromin

The RasGAP interactions that occur when neurofibromin's GAP domain and Ras are bound have two critical catalytic components. The first is the of the NF protein, which stabilizes the catalytic glutamine, as well as stabilizing the transition state of the phosphoryl transfer^[1]. The second component is the catalytic glutamine of the Ras protein, which stabilizes the nucleophilic water as it attacks the third phosphate group in the GTP molecule as shown in Figure 1.

Figure 1: The catalytic glutamine stabilizes the nucleophilic water.

Downstream Effects

Figure X; By cybertory - This file was derived from: Signal transduction v1.png, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12081090

Disease Relevance

Mutations to the neurofibromin protein are implicated in the progression of Neurofibromatosis type 1 (NF1). This condition drives several forms of human cancers by inactivating the Ras suppression effects of NF, allowing Ras to behave as an oncogene. Neurofibromatosis type 1 is an autosomal dominant disorder that affects 1 in 3,000 people, and the NF gene itself has the highest mutation rate of any known human gene, adding to its prevalence^[2]. NF1 primarily causes tumors in the central and peripheral nervous systems, but often has a multisystem expression including tumors in the dermatologic, cardiovascular, gastrointestinal, and orthopedic systems^[3]. The wide range of presentations is consistent with the multiplicity of mutations observed in the causative protein^[4]. This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.