Posttranslational Modification Defects in Fibroblast Growth Factor Receptor 1 as a Reason for Normosmic Isolated Hypogonadotropic Hypogonadism

Figure 2

The bioinformatic assays of the mutations of FGFR1 and CEP290. (a, b) (A) Conservation analysis of the two mutant sites via multiple sequence alignment. Amino acid in red color are the substitutive amino acid. Asterisks represent a high score of conservation degree. (B) The conservation degree of FGFR1 and CEP290 calculated by WebLogo software. The overall stack height represents the sequence conservation at that position, while the symbol height within the stack indicates the relative frequency of each amino or nucleic acid at that position. (c) The crystal structure of the mutation E670K upon the catalytic (tyrosine kinase) cytosolic domain of FGFR1 and the maps of the coiled-coil domain within mutant and WT CEP290. α-Helices, β-strands, and loops are colored cyan, red, and pink, respectively. Nitrogen and oxygen are colored blue and red, respectively. The mutation sites are labeled with yellow sticks. The phosphorylation site of Tyr-653 and Tyr-638 are shown as green sticks. The activation site is shown as grey sticks. Arrows point to the magnified pictures of selected residues. These structural images are shown using PyMOL.

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