9imp | pdb_00009imp
The complex of PDZ3 and PBM
Structural highlights
FunctionPARD3_RAT Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Targets the phosphatase PTEN to cell junctions.[1] [2] Publication Abstract from PubMedAs a fundamental process governing the self-renewal and differentiation of stem cells, asymmetric cell division is controlled by several conserved regulators, including the polarity protein Par3 and the microtubule-associated protein NuMA, which orchestrate the assembly and interplay of the Par3/Par6/mInsc/LGN complex at the apical cortex and the LGN/Galphai/NuMA/Dynein complex at the mitotic spindle to ensure asymmetric segregation of cell fate determinants. However, this model, which is well-supported by genetic studies, has been challenged by evidence of competitive interaction between NuMA and mInsc for LGN. Here, the solved crystal structure of the Par3/mInsc complex reveals that mInsc competes with Par6beta for Par3, raising questions about how proteins assemble overlapping targets into functional macromolecular complexes. Unanticipatedly, we discover that Par3 can recruit both Par6beta and mInsc by forming a dynamic condensate through phase separation. Similarly, the phase-separated NuMA condensate enables the coexistence of competitive NuMA and mInsc with LGN in the same compartment. Bridge by mInsc, Par3/Par6beta and LGN/NuMA condensates coacervate, robustly enriching all five proteins both in vitro and within cells. These findings highlight the pivotal role of protein condensates in assembling multi-component signalosomes that incorporate competitive protein-protein interaction pairs, effectively overcoming stoichiometric constraints encountered in conventional protein complexes. mInsc coordinates Par3 and NuMA condensates for assembly of the spindle orientation machinery in asymmetric cell division.,Huang S, Fu M, Gu A, Zhao R, Liu Z, Hua W, Mao Y, Wen W Int J Biol Macromol. 2024 Aug 30;279(Pt 2):135126. doi: , 10.1016/j.ijbiomac.2024.135126. PMID:39218187[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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