Citations

Subcellular compartmentalisation is necessary for eukaryotic cell function. Spatial and temporal regulation of kinesin activity is essential for building these local environments via control of intracellular cargo distribution. Kinesin-binding protein (KBP) interacts with a subset of kinesins via their motor domains, inhibits their microtubule (MT) attachment, and blocks their cellular function. However, its mechanisms of inhibition and selectivity have been unclear. Here we use cryo-electron microscopy to reveal the structure of KBP and of a KBP–kinesin motor domain complex. KBP is a tetratricopeptide repeat-containing, right-handed α-solenoid that sequesters the kinesin motor domain’s tubulin-binding surface, structurally distorting the motor domain and sterically blocking its MT attachment. KBP uses its α-solenoid concave face and edge loops to bind the kinesin motor domain, and selected structure-guided mutations disrupt KBP inhibition of kinesin transport in cells. The KBP-interacting motor domain surface contains motifs exclusively conserved in KBP-interacting kinesins, suggesting a basis for kinesin selectivity.

Background Anatomic total shoulder arthroplasty improves pain and function with a reported reoperation rate of approximately 1% per year. With improved glenoid fixation, reverse shoulder arthroplasty implants may outperform anatomic total shoulder arthroplasty. We evaluate the functional outcomes and reoperation rate of anatomic total shoulder arthroplasty versus reverse shoulder arthroplasty at a minimum eight-year follow-up or revision. Methods Between 2005 and 2010, 187 shoulders (137 anatomic total shoulder arthroplasty, 50 reverse shoulder arthroplasty) were retrospectively reviewed at a mean of 8.8 years. The mean age at surgery was 67 years. Females were more commonly treated with reverse shoulder arthroplasty. Both groups had similar body mass index and comorbidities. Outcome measures evaluated included abduction, forward elevation, external rotation, internal rotation, Simple Shoulder Test, Constant score, American Shoulder and Elbow Score, University of California Los Angeles Shoulder score, and Shoulder Pain and Disability Index. Results At follow-up, anatomic total shoulder arthroplasty demonstrated greater overhead range of motion and external rotation. All patient-reported outcomes remained similar between groups. Reverse shoulder arthroplasty patients were more likely to rate shoulders as much better or better after surgery (90% versus 67%, p = 0.004). Complications were observed in 24% of anatomic total shoulder arthroplasties and 8% of reverse shoulder arthroplasties (p = 0.02). Reoperation was more common in anatomic total shoulder arthroplasties (23% versus 4%, p = 0.003). Discussion At mid-to-long-term follow-up, reverse shoulder arthroplasties demonstrated significantly fewer complications and reoperations than anatomic total shoulder arthroplasties. Despite similar patient-reported outcomes, reverse shoulder arthroplasty patients were more likely to be satisfied with their shoulder.