SOS1 Ras GEF - 3D Mechanism Simulator

Loading structural data… (1NVV)

References & Databases

START HERE — how to read Ras·GDP + GTP ⇌ Ras·GTP + GDP A single nucleotide-exchange cartoon on the human SOS1 frame that exists: 1NVV (2.18 Å), SOS1 chain S, catalytic nucleotide-free H-Ras R, and allosteric H-Ras Q with GppNp (GNP) and Mg. That analog is a named occupancy on allosteric Ras, not GTP — the bridge is N3B, not O3B. Catalytic Ras starts empty. GDP and GTP are [schematic]. Glu942 is the helical-hairpin glutamate that pries the empty P-loop. GEF, not a GTPase. No EC. No hydrolysis. SOS2 is another gene. KRAS/NRAS are other genes. 1BKD is a companion, not this mesh. A-page (no covalent E~P).
Crystal structures PDB 1NVV — human SOS1·H-Ras·GppNp, 2.18 Å (Margarit 2003). Coordinates are public. GNP sits on allosteric Ras Q. Catalytic Ras R is nucleotide-free. 1BKD is a companion (nucleotide-free SOS1·H-Ras), not this mesh. SOS2 structures are other genes. HRAS and RASA1 are other pages on this path.
Mechanism — GEF exchange, not hydrolysis Margarit et al., Cell 2003, PMID:12628188 — feedback activation of SOS by Ras·GTP. UniProt Q07889 GEF. Crystal ligand on allosteric Ras is GppNp, not GTP. Product is Ras·GTP (switch on). Physiological nucleotide teaching = GTP in / GDP out — analog occupancy is allosteric, not this mesh. This page does not hydrolyse GTP. Source: Margarit 2003 · UniProt Q07889
0 — Setup: empty catalytic nucleotide site 1NVV holds SOS1, catalytic nucleotide-free H-Ras, and allosteric H-Ras·GppNp·Mg. The catalytic pocket starts empty so schematic GDP can dock. Opaque, no autoplay. GppNp on allosteric Ras is occupancy, not GTP. GEF, not a GTPase. No EC.Source: PDB 1NVV
① — Ras·GDP + GTP (reactants) The left-hand side is set up: schematic GDP docks into the catalytic nucleotide site (catalytic Ras on 1NVV is nucleotide-free → Ras·GDP), and the free GTP reactant waits on the opposite side — so both species of Ras·GDP + GTP are on screen. Crystal GppNp stays on allosteric Ras. Glu942 OE2 ⋯ Ser17 OG = 3.24 Å on this deposit. Overlay nucleotide Å are not geomClaims.Source: 1NVV empty catalytic Ras + schematic GDP/GTP
② — Helical hairpin pries the P-loop (hypothetical, lit.-based) The SOS helical hairpin (Glu942 ★) pries the empty Ras P-loop so nucleotide can leave. The protein mesh is static. This is exchange, not hydrolysis. Glu942 OE2 ⋯ Ser17 OG = 3.24 Å; Lys939 NZ ⋯ Ser17 OG = 3.49 Å; Leu938 CD2 ⋯ Ala59 CB = 3.73 Å; Thr810 O ⋯ Gly13 CA = 4.69 Å on this deposit. Slow-motion on purpose.Source: compiled GEF hairpin · Margarit 2003 PMID:12628188
③ — GDP leaves [schematic] GDP departs. The free GTP reactant is still waiting opposite, ready to enter. This is nucleotide exchange, not GTP hydrolysis — that chemistry is the HRAS page.Source: GEF net accounting · UniProt Q07889
④ — GTP enters → Ras·GTP + GDP [schematic] The free GTP (waiting since ①) enters the vacated site as the released GDP leaves — the exchange. Products on screen: Ras·GTP + GDP (net Ras·GDP + GTP ⇌ Ras·GTP + GDP). No hydrolysis. GppNp ≠ GTP. SOS2 is another gene. KRAS/NRAS are other genes. RASA1 (GAP) is a later page.Source: GEF net accounting · UniProt Q07889

How to read this page — a first-pass primer First pass: Setup (empty catalytic cleft, Glu942 ★, GppNp on allosteric Ras) → ① GDP docks + free GTP waits opposite (Ras·GDP + GTP) → ② helical hairpin pries the P-loop → ③ GDP leaves (GTP still waiting) → ④ GTP enters the vacated site → Ras·GTP + GDP. Second pass: 3.24 / 3.49 / 3.73 / 4.69 Å are crystal facts on 1NVV; GDP and GTP are [schematic]. Third pass: open “Disagreements” for GppNp ≠ GTP, GEF not GTPase, no EC, SOS2, and 1BKD.
Chemistry primer — GEF exchange, not a GTPase SOS1 exchanges GDP for GTP on Ras. It does not hydrolyse GTP. Gold H⁺ and blue nucleophile are not drawn — there is no catalytic hydrolase event on this page. Product is Ras·GTP — switch on. This is not the HRAS hydrolysis page, and not RASA1 GAP acceleration.
Words used on screen — occupancy · GEF · hairpin · SOS2 Occupancy — GppNp is the crystal ligand on allosteric Ras; never relabeled as GTP. GEF — guanine nucleotide exchange factor; no EC. Hairpin — SOS helical insert that pries the empty P-loop. SOS2 — other gene. PDB numbering = UniProt Q07889 566–1046 on SOS1; H-Ras 1–166.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1NVV (2.18 Å) with GppNp and Mg on allosteric Ras; Glu942 OE2 ⋯ Ser17 OG = 3.24 Å; Lys939 NZ ⋯ Ser17 OG = 3.49 Å; Leu938 CD2 ⋯ Ala59 CB = 3.73 Å; Thr810 O ⋯ Gly13 CA = 4.69 Å. The inferred layer ([schematic]): GDP, GTP, hairpin pry label, nucleotide leave/enter. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay nucleotide Å are not geomClaims. Allosteric Ras Y64A is named.
Disagreements on record (a) GppNp ≠ GTP. GNP on allosteric Ras is occupancy (N3B ≠ O3B). (b) GEF, not a GTPase. No EC. Do not invent 3.6.5.2. (c) Catalytic Ras is nucleotide-free on this deposit; GDP/GTP are schematic. (d) SOS2 is another gene. (e) 1BKD is a companion, not this mesh. (f) Allosteric Ras Y64A is named. (g) No protein-domain swing. Hairpin pry is a label on a static mesh. (h) No hydrolysis — that is the HRAS page. (i) KRAS / NRAS are other genes.
Regulation — allosteric Ras·GTP · isoforms · GAP Allosteric Ras·GTP feedback-activates SOS (this crystal). SOS2 is another gene. HRAS (GTPase) and RASA1 (GAP) are other pages on this path. Oncogenic Ras mutations are Regulation on the HRAS page, not this motion.Source: UniProt Q07889 · Margarit 2003 PMID:12628188
Kinetics scope (no measured timecourse on this page) One Ras·GDP + GTP ⇌ Ras·GTP + GDP event is drawn, not a steady-state run. Compiled exchange rates are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter. This page has no EC number.Source: UniProt Q07889 — no k_cat/K_m re-asserted
Sequence Human SOS1 UniProt Q07889 · NCBI Gene 6654. Screen uses 1NVV PDB-author numbering (SOS1 566–1046 = UniProt; H-Ras 1–166). SOS2 is another gene. KRAS / NRAS are other genes.
Simulation map — what you see is what is written Setup = 1NVV empty catalytic nucleotide site with GppNp on allosteric Ras (opaque, no autoplay). ① schematic GDP docks into Ras and the free GTP reactant waits opposite (Ras·GDP + GTP). ② slow-mo hairpin pry label on a static protein. ③ GDP leaves (GTP still waiting). ④ the GTP enters the vacated site → Ras·GTP + GDP. Only these events move.
Sources — bibliography of this page S1 — PDB 1NVV: human SOS1·H-Ras·GppNp, 2.18 Å — public coordinates; measured OE2⋯OG = 3.24 Å · NZ⋯OG = 3.49 Å · CD2⋯CB = 3.73 Å · O⋯CA = 4.69 Å S2 — Margarit et al., Cell 2003, PMID:12628188 — feedback activation of SOS by Ras·GTP S3 — Sequence: UniProt Q07889 (human SOS1) · NCBI Gene 6654 S4 — Kinetics: UniProt Q07889 — no EC; no k_cat/K_m re-asserted on this page

› Backbones and ligand poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., GTP identity on catalytic Ras, GDP after exchange, hairpin pry as motion), the pose is drawn schematically and labeled as such in the narration.

SOS1catalytic H-Rasallosteric H-RasON