کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5914398 1570448 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal structure of the globular domain of C1QTNF5: Implications for late-onset retinal macular degeneration
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Crystal structure of the globular domain of C1QTNF5: Implications for late-onset retinal macular degeneration
چکیده انگلیسی
Autosomal dominant late-onset retinal macular degeneration (L-ORMD) is caused by a single S163R mutation in the C1q and tumor necrosis factor-related protein 5 (C1QTNF5) gene. The C1QTNF5 gene encodes a secreted and membrane-associated protein involved in adhesion of retinal pigmented epithelial cells (RPE) to Bruch's membrane. The crystal structure of the trimeric globular domain of human C1QTNF5 at 1.34 Å resolution reveals unique features of this novel C1q family member. It lacks a Ca2+-binding site, displays a remarkable non-uniform distribution of surface electrostatic potentials and possesses a unique sequence (F181F182G183G184W185P186) that forms a hydrophobic plateau surrounded by Lys and Arg residues with a solvent cavity underneath. S163 forms a hydrogen bond with F182 in a hydrophobic area extending to the hydrophobic plateau. The pathogenic mutation S163R disrupts this hydrogen bonding and positively charges these hydrophobic areas. Thus, our analysis provides insights into the structural basis of the L-ORMD disease mechanism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 180, Issue 3, December 2012, Pages 439-446
نویسندگان
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