Xuewu Zhang's Lab UT Southwestern Medical Center
Department of Pharmacology
Department of Biochemistry

Structures of the plexin active dimer and its complex with Rap

Crystal structures reveal how dimerization drives activaton of the plexin cytoplasmic region, and how it catalyzes GTP hydrolysis for Rap by using a non-canonical mechanism. (see details in: Wang and Pascoe et al, eLife, 2013)

Autoinhibition of RhoGEFs FARP1 and FARP2

Crystal structures reveal a multi-layered autoinhibtion mechanism for the guanine nucleotide exchange factors FARP2 and its homolog FARP1. (see details in: He et al, Structure, 2013)

Plexins as RapGAPs and a structure of the plexin/Rac1 complex

This study shows that Plexins are GTPase activating proteins specific for the small GTPase Rap. The RapGAP activity is activated by induced dimerization, and Rac1 binding does not contribute to this activation process directly. (see details in: Wang, He et al, Science Signaling, 2012)

REDD1 structure: a novel fold and a functional hotspot

The functional C-terminal domain of REDD1 adopts a novel topology. Two conserved segments form a surface patch critical for function (blue in the middel panel), indicating a hotspot for binding downstream signaling protein. (see details in: Vega-Rubin-de-Celis et al, Biochemistry, 2010)

Regulation mechanism of the Plexin A3 intracellular region

The GAP domain of Plexin A3 adopts an inactive conformation (left panel), which cannot accomodate Ras in its substrate binding site (middle panel). The N-terminal segment (red) and the RBD (blue) regulate the GAP through an allosteric mechanism. (see details in: He et al, PNAS, 2009; 100: 2586-2591)

Previous Work
Inhibition of EGFR by Mig6

Mig6 inhibits the EGFR kinase by blocking the asymmetric dimer interface in the kinase domain that is crtical for activation.(see details in: Zhang et al, Nature. 2007 Nov 29;450(7170):741-4)

Activation of the EGFR kinase

EGFR activation through formation of an asymmetric dimer that mimicks the activating interaction between cyclin and CDK. (see details in: Zhang et al, Cell. 2006 Jun 16;125(6):1137-49)

B7-2/CTLA4 Complex

A molecular lattice formed by the CTLA-4/B7 complex. (see details in:Schwartz et al, Nature. 2001 Mar 29;410(6828):604-8)