Linking cell-matrix adhesions and microtubules: the role of KANK proteins

Abstract

Structure of the KANK family proteins Characteristic for the KANK family proteins is their structure with three distinct domains (Figure 3). At the N-terminus, all KANK proteins possess a highly conserved so-called KANK N-terminal (KN) domain, an α-helix with a leucine-aspartic acid (LD) motif, which mediates binding of KANK1 and 2 to talin (Bouchet et al., 2016; Sun et al., 2016; Yu et al., 2019). For KANK3 and 4 binding to talin has not been shown yet; however, due to the high conservation of the KN domains among the KANK family it is expected that KANK3 and 4 can bind to talin as well. Moreover, all KANKs possess at least one coiled coil domain located in the central region of the protein. In total there exist four different conserved coiled coil domains (CC1-4) among the KANK family, the composition of the different coiled coils differs between the four KANK paralogs (Zhu et al., 2008). Van der Vaart et al. have found that KANK coiled coil domain 1 (CC1) mediates binding to liprin-β1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, at the cell cortex in the vicinity of adhesion complexes (van der Vaart et al., 2013). At their C-terminus all KANK family members contain an ankyrin repeat domain which was shown to bind to the kinesin-4 motor protein KIF21A (Kakinuma and Kiyama, 2009; van der Vaart et al., 2013). Interestingly, the majority of studies reported that the KANK ankyrin repeat domain consists of five repeats of the ankyrin motif (Ankr1-5) (