1WER

RAS-GTPASE-ACTIVATING DOMAIN OF HUMAN P120GAP

Summary for 1WER

• Entry DOI: 10.2210/pdb1wer/pdb
• Descriptor: P120GAP (2 entities in total)
• Functional Keywords: gtpase activation, ras, gap, signal transduction, growth regulation, cancer
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P20936
• Total number of polymer chains: 1
• Total formula weight: 38223.28

Authors

Scheffzek, K.,Lautwein, A.,Kabsch, W.,Ahmadian, M.R.,Wittinghofer, A. (deposition date: 1996-11-20, release date: 1997-12-31, Last modification date: 2024-02-14)

Primary citation

Scheffzek, K.,Lautwein, A.,Kabsch, W.,Ahmadian, M.R.,Wittinghofer, A.
Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras.
Nature, 384:591-596, 1996

PubMed Abstract: Ras-related GTP-binding proteins function as molecular switches which cycle between GTP-bound 'on'- and GDP-bound 'off'-states. GTP hydrolysis is the common timing mechanism that mediates the return from the 'on' to the 'off'-state. It is usually slow but can be accelerated by orders of magnitude upon interaction with GTPase-activating proteins (GAPs). In the case of Ras, a major regulator of cellular growth, point mutations are found in approximately 30% of human tumours which render the protein unable to hydrolyse GTP, even in the presence of Ras-GAPs. The first structure determination of a GTPase-activating protein reveals the catalytically active fragment of the Ras-specific p120GAP (ref. 2), GAP-334, as an elongated, exclusively helical protein which appears to represent a novel protein fold. The molecule consists of two domains, one of which contains all the residues conserved among different GAPs for Ras. From the location of conserved residues around a shallow groove in the central domain we can identify the site of interaction with Ras x GTP. This leads to a model for the interaction between Ras and GAP that satisfies numerous biochemical and genetic data on this important regulatory process.

PubMed: 8955277
DOI: 10.1038/384591a0

Experimental method

X-RAY DIFFRACTION (1.6 Å)