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-Structure paper
タイトル | Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins. |
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ジャーナル・号・ページ | Cell, Vol. 162, Issue 4, Page 849-859, Year 2015 |
掲載日 | 2015年8月13日 |
著者 | Rui Zhang / Gregory M Alushin / Alan Brown / Eva Nogales / |
PubMed 要旨 | Microtubule (MT) dynamic instability is driven by GTP hydrolysis and regulated by microtubule-associated proteins, including the plus-end tracking end-binding protein (EB) family. We report six cryo- ...Microtubule (MT) dynamic instability is driven by GTP hydrolysis and regulated by microtubule-associated proteins, including the plus-end tracking end-binding protein (EB) family. We report six cryo-electron microscopy (cryo-EM) structures of MTs, at 3.5 Å or better resolution, bound to GMPCPP, GTPγS, or GDP, either decorated with kinesin motor domain after polymerization or copolymerized with EB3. Subtle changes around the E-site nucleotide during hydrolysis trigger conformational changes in α-tubulin around an "anchor point," leading to global lattice rearrangements and strain generation. Unlike the extended lattice of the GMPCPP-MT, the EB3-bound GTPγS-MT has a compacted lattice that differs in lattice twist from that of the also compacted GDP-MT. These results and the observation that EB3 promotes rapid hydrolysis of GMPCPP suggest that EB proteins modulate structural transitions at growing MT ends by recognizing and promoting an intermediate state generated during GTP hydrolysis. Our findings explain both EBs end-tracking behavior and their effect on microtubule dynamics. |
リンク | Cell / PubMed:26234155 / PubMed Central |
手法 | EM (らせん対称) / EM (単粒子) |
解像度 | 3.3 - 4.4 Å |
構造データ | EMDB-6347: EMDB-6348: EMDB-6349, PDB-3jak: EMDB-6350, PDB-3jal: EMDB-6351, PDB-3jar: EMDB-6352, PDB-3jat: EMDB-6353, PDB-3jas: EMDB-6354: Asymmetric (C1) reconstruction of EB3-bound microtubule (merged dataset containing tubulin bound to GTPgammaS, GMPCPP and GDP) EMDB-6355: |
化合物 | ChemComp-GTP: ChemComp-MG: ChemComp-GSP: ChemComp-G2P: ChemComp-GDP: |
由来 |
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キーワード | STRUCTURAL PROTEIN / microtubule / EB3 / GTPgammaS / kinesin / GMPCPP / GDP / seam |