title: Structural Correlation of the Neck Coil with the Coiled-coil (CC1)-Forkhead-associated (FHA) Tandem for Active Kinesin-3 KIF13A.
abstract: Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer. The reverse introduction of Pro-390 breaks the NC-CC1 coiled-coil dimer but provides the intrinsic flexibility to couple NC with the CC1-FHA tandem. Mutations of either NC, CC1, or the FHA domain all significantly impaired the motor activity. Thus, the three elements within the NC-CC1-FHA tandem of KIF13A are structurally interrelated to form a stable dimer for activating the motor. This work also provides the first direct structural evidence to support the formation of a coiled-coil neck by the short characteristic neck domain of kinesin-3.
authors.affiliation: From the National Laboratory of Biomacromolecules and.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Ren
authors.affiliation: From the National Laboratory of Biomacromolecules and.
authors.forename: Lin
authors.initials: L
authors.lastname: Huo
authors.affiliation: From the National Laboratory of Biomacromolecules and.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the National Laboratory of Biomacromolecules and.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.affiliation: From the National Laboratory of Biomacromolecules and.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: From the National Laboratory of Biomacromolecules and wfeng@ibp.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000071183:Autophagy-Related Proteins; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D018583:Pliability; D017354:Point Mutation; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020080:Tandem Repeat Sequences
chemical_list: D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; C583168:KIF13A protein, mouse; D010446:Peptide Fragments; C428743:Rb1cc1 protein, mouse; D011994:Recombinant Proteins; D016547:Kinesins
keywords: KIF13A; intracellular trafficking; kinesin; molecular motor; neck coil; structural biology; x-ray crystallography