5x1g
From Proteopedia
WHAMM's Microtubule binding motif
Structural highlights
Function[WHAMM_HUMAN] Acts as a nucleation-promoting factor (NPF) that stimulates Arp2/3-mediated actin polymerization both at the Golgi apparatus and along tubular membranes. Its activity in membrane tubulation requires F-actin and interaction with microtubules. Proposed to use coordinated actin-nucleating and microtubule-binding activities of distinct WHAMM molecules to drive membrane tubule elongation; when MT-bound can recruit and remodel membrane vesicles but is prevented to activate the Arp2/3 complex. Involved as a regulator of Golgi positioning and morphology. Participates in vesicle transport between the reticulum endoplasmic and the Golgi complex. Required for RhoD-dependent actin reorganization such as in cell adhesion and cell migration.[1] [2] [3] Publication Abstract from PubMedWASP homolog associated with actin, membranes, and microtubules (WHAMM) is a vertebrate protein functioning in membrane tubulation for intracellular membrane trafficking and specific organelle formation. Composed of multiple domains, WHAMM can bind to membrane and microtubule (MT) and promote actin polymerization nucleation. Previous work revealed that WHAMM's activity to promote actin nucleation is repressed upon binding to MTs. Here, we discovered that WHAMM interacts with alphabeta-tubulin through a small peptide motif within its MT-binding domain. We reconstructed a high-resolution structure of WHAMM's MT-binding motif (MBM) assembling around MTs using cryo-electron microscopy and verified it with chemical cross-linking and mass spectrometry analysis. We also detected a conformational switch of this motif between the non-MT-bound state and the MT-bound state. These discoveries provide new insights into the mechanism by which WHAMM coordinates actin and MT networks, the two major cytoskeletal systems involved in membrane trafficking and membrane remodeling. Structural Insights of WHAMM's Interaction with Microtubules by Cryo-EM.,Liu T, Dai A, Cao Y, Zhang R, Dong MQ, Wang HW J Mol Biol. 2017 May 5;429(9):1352-1363. doi: 10.1016/j.jmb.2017.03.022. Epub, 2017 Mar 25. PMID:28351611[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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