Rxivist logo

A designed high-affinity peptide that hijacks microtubule-based transport

By Jessica A Cross, Magda S. Chegkazi, Roberto A. Steiner, Derek N. Woolfson, Mark P Dodding

Posted 19 Jun 2020
bioRxiv DOI: 10.1101/2020.06.17.157255

Technologies that manipulate and augment the transport of vesicles and organelles by motor proteins along microtubules offer new routes to understanding its mechanistic basis, and could lead to therapeutics. Many cargoes for the kinesin-1 family of microtubule motors utilize adaptor proteins that harbor linear peptide motifs that are recognized by the tetratricopeptide repeats of kinesin light chains (KLCTPRs). These motifs bind with micromolar affinities at independent but overlapping sites. Here, we employ a fragment-linking peptide design strategy to generate an extended synthetic ligand (KinTag) with low nanomolar affinity for KLCTPRs. The X-ray crystal structure of the KLCTPR:KinTag complex demonstrates interactions as designed. Moreover, KinTag functions in cells to promote the transport of lysosomes with a high efficiency that correlates with its enhanced affinity. Together, these data demonstrate a new strategy for peptide design and its application to reveal that the more tightly a motor holds its cargo, the greater is the extent of cargo transport. ### Competing Interest Statement The authors have declared no competing interest.

Download data

  • Downloaded 230 times
  • Download rankings, all-time:
    • Site-wide: 68,088 out of 94,912
    • In synthetic biology: 783 out of 885
  • Year to date:
    • Site-wide: 17,670 out of 94,912
  • Since beginning of last month:
    • Site-wide: 7,702 out of 94,912

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)