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Thursday, 24 July, 2014

Structural basis for the extended CAP-Gly domains of p150glued binding to microtubules and the implication for tubulin dynamics

Q. Wanga, A. Crevennab, I. Kunzea, and N. Mizunoa -
PNAS, doi: 10.1073/pnas.1403135111, published online: 24 July 2014

p150glued belongs to a group of proteins accumulating at microtubule plus ends (+TIPs). It plays a key role in initiating retrograde transport by recruiting and tethering endosomes and dynein to microtubules. p150glued contains an N-terminal microtubule-binding cytoskeleton-associated protein glycine-rich (CAP-Gly) domain that accelerates tubulin polymerization. Although this copolymerization is well-studied using light microscopic techniques, structural consequences of this interaction are elusive. Here, using electron-microscopic and spectroscopic approaches, we provide a detailed structural view of p150glued CAP-Gly binding to microtubules and tubulin. Cryo-EM 3D reconstructions of p150glued-CAP-Gly complexed with microtubules revealed the recognition of the microtubule surface, including tubulin C-terminal tails by CAP-Gly. These binding surfaces differ from other retrograde initiation proteins like EB1 or dynein, which could facilitate the simultaneous attachment of all accessory components. Furthermore, the CAP-Gly domain, with its basic extensions, facilitates lateral and longitudinal interactions of tubulin molecules by covering the tubulin acidic tails. This shielding effect of CAP-Gly and its basic extensions may provide a molecular basis of the roles of p150glued in microtubule dynamics.


Article on journal's website