Part:BBa_K5036006

Vascular Endothelial Growth Factor Receptor 2 (VEGF-R2)

Part Description

It is vascular endothelial growth factor receptor which contain 3 members contain similar structures and their external parts are made up entirely of repeating segments that resemble parts of antibodies (immunoglobulin homology repeats) and they have a critical role in the formation of blood vessels and lymphatic vessels.

Usage

This is the extracellular domain of the second chain dCas9-synRTK receptor which respond specifically to vascular endothelial growth factor (VEGF) which is a specific substance for wounds so when activated it transduce the signal causing dimerization of the two receptor chains and thus help in the control of transcription and prevent auto activation.

this figure illustrates the structure of the extracellular domain of our receptor's second chain .

Literature Characterization

In this study, a group of 34 angiosarcomas were examined using immunohistochemistry technique which allowed to assess the levels of proteins involved in blood vessel growth, including vascular endothelial growth factors (VEGF-A and VEGF-C) and their corresponding receptors (VEGFR-1, VEGFR-2, and VEGFR-3).

VEGF-A was expressed by 32/34 (94%), VEGF-C by 4/34 (12%), VEGFR-1 by 32/34 (94%), VEGFR-2 by 22/34 (65%), and VEGFR-3 by 27/34 (79%) .

The figure shows immunohistochemical staining of proteins associated with blood vessel growth in angiosarcoma scalp tissue. Panel A reveals strong positivity for VEGF-A in tumor cells. Panels B and C demonstrate consistent positivity for VEGFR-1 and VEGFR-3, respectively, in the lining of tumor cells. Panel D shows VEGF-C expression within the angiosarcoma, surrounded by lighter areas containing lymphocyte immune cells.

Software Characterization

(a)Ramachandran plot

(b)VEGFR1 3d structures

this figure The Ramachandran plot shows that 93.44% of amino acid residues lie in a favorable region, indicating a well-formed protein.However, there are about 1.80% amino acid residues considered as outliers. .

This alignment plot illustrates darker green color along the diagonal line, indicating lower expected position errors between the 3D structure and the experimental structures. .

then, we measured the binding affinity and stability between VEGFR1 and VEGFA.

The alignment plot indicates a positive diagonal alignment between the 3D structure and the experimental structures which reflect favorable protein structure. .

This heatmap shows VEGFR-1 mutational landscape which is generated by EVcouplings software. It shows that the mutant variant associated with the highest epistatic fitness was (M 356 V), meanwhile the highest independent score was also related to the (M 356 V). .

Reference

Itakura, E., Yamamoto, H., Oda, Y., & Tsuneyoshi, M. (2008). Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas. Journal of surgical oncology, 97(1), 74-81.‏

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  INCOMPATIBLE WITH RFC[21]

  Illegal BglII site found at 364
  Illegal BglII site found at 1723
  
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  INCOMPATIBLE WITH RFC[1000]

  Illegal BsaI site found at 1236
  Illegal BsaI.rc site found at 46
  Illegal BsaI.rc site found at 824
  Illegal BsaI.rc site found at 2113