title: The structural basis of novel endosome anchoring activity of KIF16B kinesin.
abstract: KIF16B is a newly identified kinesin that regulates the intracellular motility of early endosomes. KIF16B is unique among kinesins in that its cargo binding is mediated primarily by the strong interaction of its PX domain with endosomal lipids. To elucidate the structural basis of this unique endosomal anchoring activity of KIF16B-PX, we determined the crystal structure of the PX domain and performed in vitro and cellular membrane binding measurements for KIF16B-PX and mutants. The most salient structural feature of KIF16B-PX is that two neighboring residues, L1248 and F1249, on the membrane-binding surface form a protruding hydrophobic stalk with a large solvent-accessible surface area. This unique structure, arising from the complementary stacking of the two side chains and the local conformation, allows strong hydrophobic membrane interactions and endosome tethering. The presence of similar hydrophobic pairs in the amino-acid sequences of other membrane-binding domains and proteins suggests that the same structural motif may be shared by other membrane-binding proteins, whose physiological functions depend on strong hydrophobic membrane interactions.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Blatner
authors.forename: Michael I
authors.initials: MI
authors.lastname: Wilson
authors.forename: Cai
authors.initials: C
authors.lastname: Lei
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Diana
authors.initials: D
authors.lastname: Murray
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Cho
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018076:DNA, Complementary; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D020349:Surface Plasmon Resonance
chemical_list: D018076:DNA, Complementary; C504670:KIF16B protein, human; D016547:Kinesins