Abnormal activation of FLT3 is closely associated with the development and progression of various tumors, particularly acute myeloid leukemia (AML), while internal tandem duplication (ITD) is a common type of FLT3 mutation.

ReadCrystal has completed the protein expression and structural resolution of the FLT3 protein target, and successfully resolved the structure of the FLT3 apo crystal (PDB ID: 1RJB). Based on these experimental conditions and stock proteins, the delivery time of the project can be shortened to 1-2 months, and the successful delivery of the project can be ensured.

FLT3 Protein

FMS-like tyrosine kinase 3 (FLT3) is a proto-oncogene belonging to the type Ⅲ receptor tyrosine kinase (RTK) family. It mediates a series of intracellular signal transduction processes and plays a key role in regulating cell proliferation and differentiation during hematopoiesis and lymphocyte proliferation. Abnormal activation of FLT3 is closely associated with the development and progression of various tumors, particularly acute myeloid leukemia (AML), while internal tandem duplication (ITD) is a common type of FLT3 mutation.

FLT3 gene mutations mainly fall into two categories:

1.Internal tandem duplication mutations in the juxtamembrane domain (FLT3-ITD): As the most common type of FLT3 mutation, FLT3-ITD accounts for approximately 65% of cases. It refers to the insertion of a tandem repeat sequence into the JMD of the gene, usually near arginine residue 595 (R595) in the JMD, which is located in exons 14 and 15. The insertion sites and sequences are highly variable, with lengths ranging from 3 to 400 base pairs (bp). Importantly, these insertions always occur in multiples of three, thereby preserving the open reading frame (ORF) of the transcript. The inserted repeat sequence causes FLT3 to dimerize and undergo continuous autophosphorylation even in the absence of ligand binding, which enhances the activation of tyrosine kinase activity. This leads to sustained activation of downstream signaling pathways (such as RAS/MAPK and PI3K/AKT), resulting in dysregulated cell proliferation and promoting the development and progression of AML.

2.Point mutations or deletions in the tyrosine kinase domain (FLT3-TKD): FLT3-TKD mutations typically occur in tyrosine kinase domain II (TKD II), often involving mutations, insertions, or deletions of amino acid residues, and are mostly located in exon 20 of the gene. Key mutation sites include D835 and I836. Similar to FLT3-ITD, FLT3-TKD mutations also trigger the activation of downstream proliferation-related pathways, thereby contributing to disease development.

Both FLT3-ITD and FLT3-TKD mutant molecules achieve activation through ligand-independent dimerization and transphosphorylation. Mutant FLT3 induces abnormal activation of multiple intracellular signaling pathways, disrupts the normal proliferation, differentiation, and apoptosis of hematopoietic cells, leads to the development of leukemia, and is associated with disease progression.

Figure 1 FTL3 Protein Structure

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FLT3 Experimental Results

Protein Purification Result(Period: In Stock/6 weeks)

Figure 2 Protein Purification Result

Crystallization and Structural Analysis(Period: 2-4 weeks)

Figure 3 Protein Crystal

Figure 4 Crystal Diffraction Pattern

Figure 5 Electron Density Map

Figure 6 FLT3 Structure