3JAR

Cryo-EM structure of GDP-microtubule co-polymerized with EB3

Summary for 3JAR

• Entry DOI: 10.2210/pdb3jar/pdb
• Related: 3JAK 3JAL 3JAS 3JAT
• EMDB information: 6351
• Descriptor: Tubulin alpha-1B chain, Tubulin beta chain, Microtubule-associated protein RP/EB family member 3, ... (6 entities in total)
• Functional Keywords: microtubule, eb3, gdp, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 14
• Total formula weight: 652347.81

Authors

Zhang, R.,Nogales, E. (deposition date: 2015-06-19, release date: 2015-08-12, Last modification date: 2024-02-21)

Primary citation

Zhang, R.,Alushin, G.M.,Brown, A.,Nogales, E.
Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins.
Cell(Cambridge,Mass.), 162:849-859, 2015

PubMed Abstract: 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.

PubMed: 26234155
DOI: 10.1016/j.cell.2015.07.012

Experimental method

ELECTRON MICROSCOPY (3.4 Å)