2kxr | pdb_00002kxr
ZO1 ZU5 domain MC/AA mutation
Structural highlights
FunctionZO1_HUMAN The N-terminal may be involved in transducing a signal required for tight junction assembly, while the C-terminal may have specific properties of tight junctions. The alpha domain might be involved in stabilizing junctions. Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells.[1] Publication Abstract from PubMedZonula occludens (ZO)-1 is a multi-domain scaffold protein known to have critical roles in the establishment of cell-cell adhesions and the maintenance of stable tissue structures through the targeting, anchoring, and clustering of transmembrane adhesion molecules and cytoskeletal proteins. Here, we report that ZO-1 directly binds to MRCKbeta, a Cdc42 effector kinase that modulates cell protrusion and migration, at the leading edge of migrating cells. Structural studies reveal that the binding of a beta hairpin from GRINL1A converts ZO-1 ZU5 into a complete ZU5-fold. A similar interaction mode is likely to occur between ZO-1 ZU5 and MRCKbeta. The interaction between ZO-1 and MRCKbeta requires the kinase to be primed by Cdc42 due to the closed conformation of the kinase. Formation of the ZO-1/MRCKbeta complex enriches the kinase at the lamellae of migrating cells. Disruption of the ZO-1/MRCKbeta complex inhibits MRCKbeta-mediated cell migration. These results demonstrate that ZO-1, a classical scaffold protein with accepted roles in maintaining cell-cell adhesions in stable tissues, also has an active role in cell migration during processes such as tissue development and remodelling. Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading edge controls cell migration.,Huo L, Wen W, Wang R, Kam C, Xia J, Feng W, Zhang M EMBO J. 2011 Feb 16;30(4):665-78. Epub 2011 Jan 14. PMID:21240187[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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