ZFIN Image: Motta et al., 2021, Fig. 3

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Figure Caption

Fig. 3

Structural impact of the p.Leu100Pro substitution in SPRED2

(A) The crystallographic complex of neurofibromin (NF1) GRD (GAPc, magenta) with the EVH1 domain of SPRED1 (blue) and GTP-bound KRAS (gray) is shown. The N- and C-terminal GAPex stretches encompassing GAPc are shown in green. The lateral chain of Leu¹⁰¹ (L101) (corresponding to Leu¹⁰⁰ in SPRED2) is shown (orange).

(B) Surface visualization (Gaussian density surface) of the hydrophobic residues close to Leu¹⁰¹ (i.e., Ala¹⁹, Val²¹, Val⁴², Trp⁹², Phe¹⁰³, and Phe¹¹²) is shown in yellow. Lateral chains of Leu¹⁰¹ and adjacent residues, Gly¹⁰⁰ (G100) and Thr¹⁰² (T102), mutated in LGSS, are shown.

(C) Enlarged view of the neurofibromin and SPRED1 interacting surfaces. Relevant residues are indicated using the single-letter amino acid code. Lateral chains of SPRED1 residues (Arg²⁴, Gly³⁰, Trp³¹, Val⁴⁴, Gly⁶², Thr⁸⁸, Trp⁹², Gly¹⁰⁰, and Thr¹⁰²) mutated in LGSS are shown (yellow), together with Leu¹⁰¹ (orange). Of note, Thr¹⁰² interacts with both GAPc (Leu¹²⁵²) and GAPex (Met¹²¹⁵).

Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Am. J. Hum. Genet.