Tubulin–RB3 protein complex

The **tubulin–RB3 protein complex** is a protein assembly formed by αβ-tubulin heterodimers and the stathmin-like domain (SLD) of the neural RB3 protein, a member of the stathmin phosphoprotein family. This complex is characterized by a curved structure, mimicking the conformation of tubulin during microtubule depolymerization. The RB3 helix binds two tubulin dimers, sequestering them and thereby preventing their assembly into microtubules[5][6]. The interaction regulates microtubule dynamics and is crucial in processes like cell division and neuronal growth. The complex harbors structurally characterized drug-binding sites, notably the colchicine site and a recently identified Tumabulin site at the interface of tubulin and RB3[1]. Small molecules targeting these sites can act as microtubule inhibitors or “molecular glues,” and serve as leads for new anticancer agents, particularly in cancer types that overexpress RB3[1][3][5]. RB3 and its wider stathmin family (including SCG10, SCLIP, and others) regulate intracellular microtubule dynamics, and their role in health and disease is linked to their ability to destabilize microtubules by sequestering tubulin[4]. The tubulin–RB3 complex is thus a structurally validated and mechanistically important therapeutic target in cancer and potentially in other proliferative or neurological disorders.

Other names

Tubulin–RB3 complexTubulin:stathmin-like domain (SLD) complexT2R complexTubulin:RB3-SLD complex

Inhibition of microtubule assembly (by stabilizing the tubulin–RB3 curved complex and acting as microtubule depolymerizers); “Molecular glue” action (strengthening the tubulin–RB3 interaction, enhancing depolymerization activity)