کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4498269 1318974 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The comparison of VEGFR-1-binding domain of VEGF-A with modelled VEGF-C sheds light on receptor specificity
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
The comparison of VEGFR-1-binding domain of VEGF-A with modelled VEGF-C sheds light on receptor specificity
چکیده انگلیسی

Receptor specificity determines the role of vascular endothelial growth factors (VEGFs), which either induce angiogenesis via VEGFR-1 and VEGFR-2 receptors or lymphangiogenesis via the VEGFR-3 receptor. Among the VEGFs, VEGF-A and VEGF-B predominantly induce angiogenesis while VEGF-C and VEGF-D induce lymphangiogenesis. The answer for the question of why VEGF-C and VEGF-D are not able to bind VEGFR-1 and behave as angiogenic growth factors may hide behind the details of the tertiary structures of these proteins. In the present study, the tertiary structure of human VEGF-C protein was modelled and the model was compared with the known human VEGF-A tertiary structure. In overall, the modelled structure highly resembled the structure of VEGF-A. The respective key residues that are involved in cysteine-knot motif formation in VEGF-A are similarly located and identically oriented in VEGF-C, indicating the presence of a VEGF-A-like homodimer. However, a VEGF-C homodimer created via monomer docking did not superimpose well with the VEGF-A homodimer. Rigid docking models of VEGF-C with the VEGFR-1 receptor revealed that in the VEGF-C–VEGFR-1 complex, the receptor–protein-interacting residues were not correctly oriented to induce angiogenesis via VEGFR-1. Mapping the electrostatic surface potentials to the protein surfaces revealed noteworthy number of dissimilarities between VEGF-A and VEGF-C, indicating that overall both proteins differ in their folding properties and stability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 253, Issue 3, 7 August 2008, Pages 446–451
نویسندگان
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