Tubulin alpha-beta heterodimer interface

The Tubulin alpha-beta heterodimer interface is a critical structural and regulatory site within the tubulin heterodimer, the fundamental building block of microtubules [1]. This interface contains several distinct drug-binding pockets, most notably the colchicine site (intra-dimer) and the vinca alkaloid site (inter-dimer) [2]. Binding of small molecules to these sites prevents the proper longitudinal or lateral association of tubulin dimers, thereby inhibiting microtubule polymerization and disrupting microtubule dynamics [3]. Such disruption prevents the formation of a functional mitotic spindle, triggering the spindle assembly checkpoint and leading to mitotic arrest and subsequent apoptosis [4]. Clinically, this interface is a major therapeutic target for a variety of cancers and is also targeted by drugs like colchicine to treat inflammatory conditions such as gout by inhibiting leukocyte migration [5]. Sources: [1] UniProt (P07437, P68363); [2] Lu et al., Pharm Res 2012; [3] Jordan & Wilson, Nat Rev Cancer 2004; [4] StatPearls, Vinca Alkaloids; [5] PubChem, Colchicine.

Other names

Alpha-beta tubulin dimer interfaceTubulin heterodimer interfaceColchicine binding siteVinca alkaloid binding siteIntra-dimer tubulin interfaceInter-dimer tubulin interface

Inhibition of microtubule polymerization by binding to the alpha-beta tubulin interface, leading to mitotic arrest and apoptosis.