The coiled-coil helix in the neck of kinesin.

Kinesin is a microtubule-dependent motor protein. We have recently determined the X-ray structure of monomeric and dimeric kinesin from rat brain. The dimer consists of two motor domains, held together by their alpha-helical neck domains forming a coiled coil. Here we analyze the nature of the interactions in the neck domain (residues 339-370). Overall, the neck helix shows a heptad repeat (abcdefg)n typical of coiled coils, with mostly nonpolar residues in positions a and d. However, the first segment (339-355) contains several nonclassical residues in the a and d positions which tend to weaken the hydrophobic interaction along the common interface. Instead, stabilization is achieved by a hydrophobic "coat" formed by the a and d residues and the long aliphatic moieties of lysines and glutamates, extending away from the coiled-coil core. By contrast, the second segment of the kinesin neck (356-370) shows a classical leucine zipper pattern in which most of the hydrophobic residues are buried at the highly symmetrical dimer interface. The end of the neck reveals the structure of a potential coiled-coil "trigger" sequence.

[1]  C. Mant,et al.  α-Helical Protein Assembly Motifs* , 1997, The Journal of Biological Chemistry.

[2]  D A Parry,et al.  Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. , 1990, Proteins: Structure, Function, and Bioinformatics.

[3]  D. Parry,et al.  α‐Helical coiled coils and bundles: How to design an α‐helical protein , 1990 .

[4]  D A Winkelmann,et al.  Three-dimensional structure of myosin subfragment-1: a molecular motor. , 1993, Science.

[5]  R. Fletterick,et al.  Three-dimensional structure of the motor domain of NCD, a kinesin-related motor with reversed polarity of movement , 1996 .

[6]  M. Steinmetz,et al.  A distinct 14 residue site triggers coiled‐coil formation in cortexillin I , 1998, The EMBO journal.

[7]  F Arisaka,et al.  Identification of kinesin neck region as a stable alpha-helical coiled coil and its thermodynamic characterization. , 1997, Biochemistry.

[8]  E. Mandelkow,et al.  Crystallization and preliminary X-ray analysis of the single-headed and double-headed motor protein kinesin. , 1997, Journal of structural biology.

[9]  T. Alber Structure of the leucine zipper , 1992, Current Biology.

[10]  A. Lupas,et al.  Predicting coiled coils from protein sequences , 1991, Science.

[11]  A. Lupas Coiled coils: new structures and new functions. , 1996, Trends in biochemical sciences.

[12]  Crystal structure of the kinesin motor domain reveals a structural similarity to myosin , 1996 .

[13]  B. Berger,et al.  Predicting coiled coils by use of pairwise residue correlations. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Johnson,et al.  Alternating site mechanism of the kinesin ATPase. , 1998, Biochemistry.

[15]  F. Crick,et al.  The packing of α‐helices: simple coiled‐coils , 1953 .

[16]  P. S. Kim,et al.  X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. , 1991, Science.

[17]  Vincent A. Fischetti,et al.  Identifying Periodic Occurrences of a Template with Applications to Protein Structure , 1993, Inf. Process. Lett..

[18]  R. Cross,et al.  Weak and strong states of kinesin and ncd. , 1996, Journal of molecular biology.

[19]  Wei Jiang,et al.  Influence of the Kinesin Neck Domain on Dimerization and ATPase Kinetics* , 1997, The Journal of Biological Chemistry.

[20]  K. Holmes The swinging lever-arm hypothesis of muscle contraction , 1997, Current Biology.

[21]  E. Mandelkow,et al.  X-ray structure of motor and neck domains from rat brain kinesin. , 1997, Biochemistry.

[22]  Kenneth H. Downing,et al.  Structure of the αβ tubulin dimer by electron crystallography , 1998, Nature.

[23]  P. Y. Chou,et al.  Prediction of the secondary structure of proteins from their amino acid sequence. , 2006 .

[24]  R J Fletterick,et al.  The design plan of kinesin motors. , 1997, Annual review of cell and developmental biology.

[25]  R. Hodges,et al.  Demonstration of Coiled-Coil Interactions within the Kinesin Neck Region Using Synthetic Peptides , 1997, The Journal of Biological Chemistry.

[26]  J. Correia,et al.  Sedimentation studies on the kinesin motor domain constructs K401, K366, and K341. , 1995, Biochemistry.

[27]  E. Mandelkow,et al.  Interaction of monomeric and dimeric kinesin with microtubules. , 1998, Journal of molecular biology.

[28]  J. Gelles,et al.  Failure of a single-headed kinesin to track parallel to microtubule protofilaments , 1995, Nature.

[29]  R. Hodges,et al.  Relationship of sidechain hydrophobicity and alpha-helical propensity on the stability of the single-stranded amphipathic alpha-helix. , 1995, Journal of peptide science : an official publication of the European Peptide Society.

[30]  E. Mandelkow,et al.  Image Reconstructions of Microtubules Decorated with Monomeric and Dimeric Kinesins: Comparison with X-Ray Structure and Implications for Motility , 1998, The Journal of cell biology.

[31]  A. Lupas,et al.  Predicting coiled-coil regions in proteins. , 1997, Current opinion in structural biology.

[32]  E. Mandelkow,et al.  The Crystal Structure of Dimeric Kinesin and Implications for Microtubule-Dependent Motility , 1997, Cell.

[33]  B. Rost,et al.  Prediction of protein secondary structure at better than 70% accuracy. , 1993, Journal of molecular biology.