4RUG

Cyrstal structure of SLIT-ROBO Rho GTPase-activating protein 2 fragment

Summary for 4RUG

• Entry DOI: 10.2210/pdb4rug/pdb
• Related: 4RTT
• Descriptor: SLIT-ROBO Rho GTPase-activating protein 2 (2 entities in total)
• Functional Keywords: srgap2, sh3, ligand binding, robo1, nuclear, plasma membrane, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: O75044
• Total number of polymer chains: 2
• Total formula weight: 20542.80

Authors

Opatowsky, Y.,Guez-Hadad, J. (deposition date: 2014-11-19, release date: 2015-11-04, Last modification date: 2024-02-28)

Primary citation

Guez-Haddad, J.,Sporny, M.,Sasson, Y.,Gevorkyan-Airapetov, L.,Lahav-Mankovski, N.,Margulies, D.,Radzimanowski, J.,Opatowsky, Y.
The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism.
Structure, 23:1989-2000, 2015

PubMed Abstract: srGAP proteins regulate cell migration and morphogenesis by shaping the structure and dynamics of the cytoskeleton and membranes. First discovered as intracellular effectors for the Robo1 axon-guidance receptor, srGAPs were later identified as interacting with several other nuclear and cytoplasmic proteins. In all these cases, the srGAP SH3 domain mediates protein-protein interactions by recognizing a short proline-rich segment on the cognate-binding partner. However, as interactions between the isolated SH3 domain and a selected set of ligands show weak affinity and low specificity, it is not clear how srGAPs are precisely recruited to their signaling sites. Here, we report a two-component molecular mechanism that regulates ligand binding to srGAP2 by on the one hand dramatically tightening their association and on the other, moderately autoinhibiting and restricting binding. Our results allow the design of point mutations for better probing of srGAP2 activities, and may facilitate the identification of new srGAP2 ligands.

PubMed: 26365803
DOI: 10.1016/j.str.2015.08.009

Experimental method

X-RAY DIFFRACTION (1.73 Å)