Dimerization is necessary for MIM-mediated membrane deformation and endocytosis.
MIM [missing in metastasis; also called MTSS1 (metastasis suppressor 1)] is an intracellular protein that binds to actin and cortactin and has an intrinsic capacity to sense and facilitate the formation of protruded membranous curvatures implicated in cellular polarization, mobilization and endocytosis. The N-terminal 250 amino acids of MIM undergo homodimerization and form a structural module with the characteristic of an I-BAR [inverse BAR (Bin/amphiphysin/Rvs)] domain. To discern the role of the dimeric configuration in the function of MIM, we designed several peptides able to interfere with MIM dimerization in a manner dependent upon their lengths. Overexpression of one of the peptides effectively abolished MIM-mediated membrane protrusions and transferrin uptake. However, a peptide with a high potency inhibiting MIM dimerization failed to affect its binding to actin and cortactin. Thus the results of the present study indicate that the dimeric configuration is essential for MIM-mediated membrane remodelling and serves as a proper target to develop antagonists specifically against an I-BAR-domain-containing protein.
School of Chemistry and Chemical Engineering, Southeast University, 87 Dingjia Bridge Road, Nanjing 210096, China.
Meng
M
Cao
Tailan
T
Zhan
Min
M
Ji
Xi
X
Zhan
D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D004705:Endocytosis / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization
D008840:Microfilament Proteins