Introduction

Neurofibromin is a protein that is coded for by the NF1 gene which is located on chromosome 17. It functions as a tumor suppressor gene through its association with the protein Ras.

Structure

Neurofibromin is a homodimer made up of two identical chains. There are two conformations that classify neurofibromin known as its open and closed conformations. These conformations allow neurofibromin to associate with the protein Ras and perform its function of Ras regulation. The transformation between the overall closed conformation and open conformation of neurofibromin signifies a transition between an active neurofibromin protein and an inactive neurofibromin protein. There are two important domains involved in the transition between the open and close conformations, the GRD and the Sec14-PH domain. Although neurofibromin is a homodimer with two identical protomers, only one protomer needs to have its GRD and Sec14-PH domains rotated in the open conformation in order for it to be able to perform its function.

Closed Conformation

Open Conformation

Function

Neurofibromin functions as a tumor suppressor protein. Its job is to prevent cell growth by turning off another protein known as Ras which in its active state, stimulates cell growth and division. Ras is a GTPase membrane protein that can only interact with Neurofibromin, a cytoplasmic protein, in the open conformation. This interaction occurs via an arginine finger (R1276) present in the GRD of Neurofibromin.

Disease

Structural highlights

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