5NR4

Crystal structure of Clasp2 TOG1 domain

Summary for 5NR4

• Entry DOI: 10.2210/pdb5nr4/pdb
• Descriptor: CLIP-associating protein 2 (2 entities in total)
• Functional Keywords: microtubules, tog domain, tubulin, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 51508.13

Authors

Sharma, A.,Olieric, N.,Weinert, T.,Olieric, V.,Steinmetz, M.O. (deposition date: 2017-04-21, release date: 2018-05-30, Last modification date: 2024-05-08)

Primary citation

Aher, A.,Kok, M.,Sharma, A.,Rai, A.,Olieric, N.,Rodriguez-Garcia, R.,Katrukha, E.A.,Weinert, T.,Olieric, V.,Kapitein, L.C.,Steinmetz, M.O.,Dogterom, M.,Akhmanova, A.
CLASP Suppresses Microtubule Catastrophes through a Single TOG Domain.
Dev. Cell, 46:40-58.e8, 2018

PubMed Abstract: The dynamic instability of microtubules plays a key role in controlling their organization and function, but the cellular mechanisms regulating this process are poorly understood. Here, we show that cytoplasmic linker-associated proteins (CLASPs) suppress transitions from microtubule growth to shortening, termed catastrophes, including those induced by microtubule-destabilizing agents and physical barriers. Mammalian CLASPs encompass three TOG-like domains, TOG1, TOG2, and TOG3, none of which bind to free tubulin. TOG2 is essential for catastrophe suppression, whereas TOG3 mildly enhances rescues but cannot suppress catastrophes. These functions are inhibited by the C-terminal domain of CLASP2, while the TOG1 domain can release this auto-inhibition. TOG2 fused to a positively charged microtubule-binding peptide autonomously accumulates at growing but not shrinking ends, suppresses catastrophes, and stimulates rescues. CLASPs suppress catastrophes by stabilizing growing microtubule ends, including incomplete ones, preventing their depolymerization and promoting their recovery into complete tubes. TOG2 domain is the key determinant of these activities.

PubMed: 29937387
DOI: 10.1016/j.devcel.2018.05.032

Experimental method

X-RAY DIFFRACTION (1.198 Å)