---
pmid: '12787671'
title: Structural fingerprints of the Ras-GTPase activating proteins neurofibromin
  and p120GAP.
authors:
- Ahmadian MR
- Kiel C
- Stege P
- Scheffzek K
journal: J Mol Biol
year: '2003'
full_text_available: false
doi: 10.1016/s0022-2836(03)00514-x
pubmed_publication_types:
- Comparative Study
- Journal Article
publication_type: PRIMARY_RESEARCH
---

# Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and p120GAP.
**Authors:** Ahmadian MR, Kiel C, Stege P, Scheffzek K
**Journal:** J Mol Biol (2003)
**DOI:** [10.1016/s0022-2836(03)00514-x](https://doi.org/10.1016/s0022-2836(03)00514-x)

## Abstract

1. J Mol Biol. 2003 Jun 13;329(4):699-710. doi: 10.1016/s0022-2836(03)00514-x.

Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and
p120GAP.

Ahmadian MR(1), Kiel C, Stege P, Scheffzek K.

Author information:
(1)Department Structural Biology, Max-Planck-Institute for Molecular Physiology,
Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.

Ras specific GTPase activating proteins (GAPs), neurofibromin and p120GAP, bind
GTP bound Ras and efficiently complement its active site. Here we present
comparative data from mutations and fluorescence-based assays of the catalytic
domains of both RasGAPs and interpret them using the crystal structures. Three
prominent regions in RasGAPs, the arginine-finger loop, the
phenylalanine-leucine-arginine (FLR) region and alpha7/variable loop contain
structural fingerprints governing the GAP function. The finger loop is crucial
for the stabilization of the transition state of the GTPase reaction. This
function is controlled by residues proximal to the catalytic arginine, which are
strikingly different between the two RasGAPs. These residues specifically
determine the orientation and therefore the positioning of the arginine finger
in the Ras active site. The invariant FLR region, a hallmark for RasGAPs,
indirectly contributes to GTPase stimulation by forming a scaffold, which
stabilizes Ras switch regions. We show that a long hydrophobic side-chain in the
FLR region is crucial for this function. The alpha7/variable loop uses several
conserved residues including two lysine residues, which are involved in numerous
interactions with the switch I region of Ras. This region determines the
specificity of the Ras-RasGAP interaction.

DOI: 10.1016/s0022-2836(03)00514-x
PMID: 12787671 [Indexed for MEDLINE]