PDBsum entry 4rtt

Protein binding

PDB id: 4rtt

Contents

Protein chains

80 a.a.

80 a.a.

Ligands

SO4 ×3

Waters ×71

PDB id:

4rtt

Name:

Protein binding

Title:

Cyrstal structure of slit-robo rho gtpase-activating protein 2 fragment

Structure:

Slit-robo rho gtpase-activating protein 2. Chain: a, b. Fragment: unp residues 729-815. Synonym: srgap2, formin-binding protein 2, rho gtpase-activating protein 34. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: srgap2, arhgap34, fnbp2, kiaa0456, srgap2a. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.87Å R-factor: 0.223 R-free: 0.259

Authors:

Y.Opatowsky,J.Guez-Hadad

Key ref:

J.Guez-Haddad et al. (2015). The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism. Structure, 23, 1989-2000. PubMed id: 26365803 DOI: 10.1016/j.str.2015.08.009

Date:

16-Nov-14 Release date: 04-Nov-15

Protein chain

O75044  (SRGP2_HUMAN) -  SLIT-ROBO Rho GTPase-activating protein 2 from Homo sapiens

Seq: 1071 a.a.

Struc: 80 a.a.*

Protein chain

O75044  (SRGP2_HUMAN) -  SLIT-ROBO Rho GTPase-activating protein 2 from Homo sapiens

Seq: 1071 a.a.

Struc: 80 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1016/j.str.2015.08.009

Structure 23:1989-2000 (2015)

PubMed id: 26365803

The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism.

J.Guez-Haddad, M.Sporny, Y.Sasson, L.Gevorkyan-Airapetov, N.Lahav-Mankovski, D.Margulies, J.Radzimanowski, Y.Opatowsky.

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.