Recombinant Human KRAS protein

KRAS recombinant protein is a genetically engineered form of the KRAS oncoprotein, widely studied for its pivotal role in cellular signaling and cancer biology. The KRAS gene encodes a small GTPase that acts as a molecular switch, cycling between active GTP-bound and inactive GDP-bound states to regulate pathways controlling cell proliferation, survival, and differentiation. Mutations in KRAS, commonly at codons 12. 13. or 61. lock the protein in a constitutively active GTP-bound state, leading to uncontrolled signaling through effectors like RAF-MEK-ERK and PI3K-AKT. These mutations occur in approximately 20–25% of human cancers, with high prevalence in pancreatic, colorectal, and non-small cell lung cancers. Historically, KRAS was deemed "undruggable" due to its smooth surface and picomolar affinity for GTP, complicating direct targeting.

Recombinant KRAS proteins are produced in vitro using expression systems (e.g., E. coli, mammalian cells) for structural and functional studies. They enable detailed characterization of mutant-specific behaviors, interactions with regulators (GAPs, GEFs), and effectors. For example, KRAS G12C recombinant proteins have been instrumental in developing covalent inhibitors like sotorasib and adagrasib, which target the mutant cysteine residue. These proteins also aid in elucidating resistance mechanisms and screening novel therapeutics. Recent advancements in structural biology, supported by recombinant KRAS, have revealed cryptic binding pockets and allosteric sites, expanding opportunities for drug discovery. Additionally, they facilitate biophysical assays (e.g., SPR, ITC) to measure binding kinetics and drug efficacy. Despite progress, challenges persist in targeting non-G12C mutants, driving ongoing research into pan-KRAS inhibitors and combination therapies. Recombinant KRAS remains a cornerstone in understanding oncogenic signaling and bridging translational gaps in precision oncology.