| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2029892 | Structure | 2010 | 11 Pages |
SummaryThe RZZ complex recruits dynein to kinetochores. We investigated structure, topology, and interactions of the RZZ subunits (ROD, ZWILCH, and ZW10) in vitro, in vivo, and in silico. We identify neuroblastoma-amplified gene (NAG), a ZW10 binder, as a ROD homolog. ROD and NAG contain an N-terminal β propeller followed by an α solenoid, which is the architecture of certain nucleoporins and vesicle coat subunits, suggesting a distant evolutionary relationship. ZW10 binding to ROD and NAG is mutually exclusive. The resulting ZW10 complexes (RZZ and NRZ) respectively contain ZWILCH and RINT1 as additional subunits. The X-ray structure of ZWILCH, the first for an RZZ subunit, reveals a novel fold distinct from RINT1's. The evolutionarily conserved NRZ likely acts as a tethering complex for retrograde trafficking of COPI vesicles from the Golgi to the endoplasmic reticulum. The RZZ, limited to metazoans, probably evolved from the NRZ, exploiting the dynein-binding capacity of ZW10 to direct dynein to kinetochores.
► The ZW10 protein is shown to be part of two structurally related complexes, the RZZ and the NRZ ► ROD and NAG, subunits of the RZZ and NRZ, respectively, consist of a β propeller and an α solenoid ► This organization is typical of clathrin, COP-I, and nucleoporins, suggesting the RZZ evolved from them ► A crystal structure of ZWILCH, an RZZ subunit, is reported and shown to have a novel fold
