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Crystal structure of CLASP2 TOG4 fused with LL5beta
Structural highlights
FunctionCLAP2_HUMAN Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.[1] [2] [3] [4] [5] [6] [7] PHLB2_HUMAN Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity).[8] Publication Abstract from PubMedMicrotubule organization in cells relies on targeting mechanisms. Cytoplasmic linker proteins (CLIPs) and CLIP-associated proteins (CLASPs) are key regulators of microtubule organization, yet the underlying mechanisms remain elusive. Here, we reveal that the C-terminal domain of CLASP2 interacts with a common motif found in several CLASP-binding proteins. This interaction drives the dynamic localization of CLASP2 to distinct cellular compartments, where CLASP2 accumulates in protein condensates at the cell cortex or the microtubule plus end. These condensates physically contact each other via CLASP2-mediated competitive binding, determining cortical microtubule targeting. The phosphorylation of CLASP2 modulates the dynamics of the condensate-condensate interaction and spatiotemporally navigates microtubule growth. Moreover, we identify additional CLASP-interacting proteins that are involved in condensate contacts in a CLASP2-dependent manner, uncovering a general mechanism governing microtubule targeting. Our findings not only unveil a tunable multiphase system regulating microtubule organization, but also offer general mechanistic insights into intricate protein-protein interactions at the mesoscale level. CLASP-mediated competitive binding in protein condensates directs microtubule growth.,Jia X, Lin L, Guo S, Zhou L, Jin G, Dong J, Xiao J, Xie X, Li Y, He S, Wei Z, Yu C Nat Commun. 2024 Aug 2;15(1):6509. doi: 10.1038/s41467-024-50863-3. PMID:39095354[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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