A novel solid-state nanopore sensing technique is described to study vascular endothelial growth factor (VEGF). VEGF is a cytokine that stimulates vascularization and is used as a cancer biomarker. Its biological activity depends on the isomerization state. Dimeric VEGF facilitates dimerization of the VEGF receptor which initiates the signal transduction pathway. Monomeric VEGF consists of two domains; a VEGF receptor recognition domain and a heparin binding domain, separated by a peptide sequence cleavable by plasmin. Translocation of VEGF through a 4 to 6 nm-diameter pore, fabricated via transmission electron microscope sculpting on an thinned 10 nm free-standing SiN membrane, produces a structural-dependent electronic signature. By fine-tuning the pore's geometry and experimental conditions, VEGF translocation consistently produces multi-step patterns, which are used to differentiate monomeric and dimeric isoforms. The equilibrium dissociation constant depends on concentration and pH. Further study with TCEP and plasmin show that the step pattern corresponds to the translocation of individual protein domains. These results demonstrate the potential for nanopores to detect small proteins and its capability to resolve the higher-order structure of proteins at the single-molecule level.