A putative structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in mammalian plexin regulation
- Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, China
- Beijing Computational Science Research Center, China
- Department of Pharmacology, University of Texas Southwestern Medical Center, United States
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, China
- Antidote Health Foundation for Cure of Cancer, United States
Figures
Figure 1 with 1 supplement
Plexin architecture, dimerization, and GTPase binding of the RBD domain.
(A) Components of a plexin molecule. Each RBD domain is connected with a GAP domain by the N and C linkers. (B) Architecture of the semaphorin-induced plexin dimer. A buttress segment is positioned …
Figure 1—figure supplement 1
RhoD binding with plexin RBD domain and anchoring to the membrane.
As shown, an RBD-bound RhoD is anchored to the membrane in our simulations by embedding the palmitoylated Cys207 at the C-terminal tail of the RhoD into the membrane.
Figure 2 with 1 supplement
Crystal structure of the RhoD/plexin B2-RBD complex.
(A) Overall structure of the RhoD/plexin B2-RBD complex based on the domain-swapped dimeric structure (Figure 1—figure supplement 1). The structure of RND1/plexin B1-RBD complex (PDB ID: 2REX) is …
Figure 2—figure supplement 1
Two orthogonal views of the asymmetric unit of the RhoD/plexin B2-RBD complex crystal.
The two copies of the RBD, colored blue and cyan, respectively, form a domain-swapped dimer, which binds two RhoD molecules (magenta).
Figure 3 with 1 supplement
Plexin-bound RND1 and RhoD interact with the membrane differently.
(A, B) Representative snapshots of the simulations of RND1- and RhoD-bound plexin dimer. (C) Close-up view of the membrane interaction of RhoD bound with the plexin dimer. Primarily the membrane …
Figure 3—figure supplement 1
Additional data on RND1/RhoD-membrane contact and charged lipid enrichment.
(A) Distributions of the membrane contact area of RND1 and RhoD bound with the plexin dimer. The data was from three simulations each of the RND1- and RhoD-bound dimers; each system contained two …
Figure 4 with 1 supplement
RND1- and RhoD-bound RBD domains are positioned differently with respect to their respective GAP domains.
(A) RhoD-bound plexin dimer. (B) A close-up of a part of the plexin dimer illustrating the relative positions of the membrane, the RhoD (or RND1) GTPase (purple), the RBD domain (blue), the GAP …
Figure 4—figure supplement 1
Additional data on root mean square deviation (RMSD) and domain-domain contact.
(A) The RBD contact area with RND1 and RhoD, and RMSD of the RND1 and RhoD catalytic domains with the RBD domains aligned from three 1-μs simulations each for RND1- and RhoD-bound plexin dimer. (B) …
Figure 5 with 1 supplement
Interaction between the buttress segment and the dimerization helices.
(A) RhoD- or RND1-bound plexin dimer. (B) Close-up of the RND1-bound dimer centered at the dimerization helices (yellow). The buttress segments (red), Helix 11 (green), the RBD domains (blue), the N …
Figure 5—figure supplement 1
Additional data on root mean square deviation (RMSD) and the buttress-dimerization helices contact.
(A) Contact area of the buttress segment with the dimerization helix in three simulations each for RBD-free, RND1-bound, RhoD-bound dimers, and for plexin monomer. (B) The RMSDs of the dimerization …
Figure 6
The charge distribution at the putative membrane interface of Rho-family GTPases.
(A) Sequence alignment of Rho-family GTPases at the region of the putative membrane interface; red denotes negatively charged residues, and blue denotes positively charged residues. All members of …
Additional files
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Supplementary file 1
Diffraction data and refinement statistics of the crystal structure.
- https://cdn.elifesciences.org/articles/64304/elife-64304-supp1-v2.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/64304/elife-64304-transrepform-v2.docx
