The PAZ domain of the Argonaute protein CSR-1b plays a critical role in chromosome segregation during C. elegans development. This study demonstrates that replacing the native CSR-1 PAZ domain with that of the WAGO-1 Argonaute protein results in severe phenotypic defects, including significantly reduced fertility, chromosome segregation abnormalities, and an altered sex ratio characterized by an increased proportion of male progeny. These phenotypes are consistent with a disruption of normal CSR-1 function. The CSR-1(WAGO-PAZ) chimera likely interferes with endogenous CSR-1 activity by competing for small RNAs or by disrupting the formation of functional complexes required for its nuclear role. Molecular dynamics simulations reveal a subtle but significant structural deviation in the chimeric PAZ domain compared to the AlphaFold prediction, suggesting that the WAGO-1 PAZ domain adopts a distinct conformation within the CSR-1 context. This structural incompatibility may underlie the functional impairment observed. Together, these findings establish the PAZ domain of CSR-1b as a key determinant of its function in chromosome segregation and highlight the importance of precise domain architecture for proper Argonaute protein activity.