Fig. 1.

Crystal structure of the dynein microtubule-binding domain. (A) Cartoon of a dynein motor (heavy chain). A gray box highlights the region of the stalk and microtubule-binding domain (MTBD) whose atomic structure is reported. (B) Effect of different heptad registries on microtubule-binding affinity of monomeric SRS-MTBD fusions with stalks of one-quarter and full native length. Paired numbers designating each construct (e.g., 22:19) indicate the number of residues between the SRS splice site and the proline marking the stalk-MTBD boundary for CC1 and CC2, respectively. (C) Crystal structure of the MTBD, showing the two α helices of the stalk (CC1, purple; CC2, red) that extend out of the SRS coiled coil and connect to the six-helix bundle (H1 to H6) forming the MTBD proper. A staggered pair of conserved prolines (Pro³²⁸⁵ and Pro³⁴⁰⁹) are associated with a kink in the stalk. Inset: dimeric SRS-MTBD fusion protein (chain A, blue SRS with red MTBD; chain B, gray). (D) Schematic diagram of the stalk helices (CC1 and CC2) showing the heptad repeat hydrophobic contacts (blue lines) in the core of the coiled coil. The regularity of this repeat is disrupted between the conserved prolines (magenta), resulting in a half-heptad shift in coiled-coil registry. Residues in the SRS are shown in green. Residues in CC1 and CC2 that contact the other helices in MTBD are marked with red dots Abbreviations: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; Y, Tyr.