Biology subjects

Asenjo, A.

Publications and source records attributed to Asenjo, A..

3 recordsLinked to original sources

bioRxiv2025

Pathogenic KIF1A R350 Variants Disrupt A Conserved Kinesin-Tubulin Salt Bridge

Pathogenic variants in the motor domain of the kinesin-3 motor protein KIF1A cause a range of neurodevelopmental and neurodegenerative conditions collectively termed KIF1A-associated neurological disorder (KAND). Among these, mutations at residue R350 are linked to hereditary spastic paraplegia and altered motor function. Yet, the structural basis for their pathogeny remains unclear. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of KIF1A R350G and R350W bound to microtubules in both the apo and AMP-PNP-bound states. We identify a previously unrecognized salt bridge between KIF1A residue R350 and -tubulin E415 that is disrupted in both mutants. This loss of electrostatic interaction correlates with increased velocity and reduced processivity, as demonstrated by single-molecule assays. Our results reveal a conserved electrostatic interaction at the motor-microtubule interface that regulates KIF1As motility behavior.

biochemistry↗

bioRxiv2025

Geographical variation in mitogenomes of the largetooth sawfish Pristis pristis: challenges and perspectives for conservation efforts

Sawfishes (Pristidae) have been severely impacted by coastal development and unregulated fisheries and are considered Critically Endangered by the IUCN Red List. Environmental DNA (eDNA) analyses have shown potential for monitoring elasmobranch species, with various studies focusing on using species-specific approaches to detect Pristis species. However positive detection using existing probes has not been confirmed in some geographic regions where they would be expected. Here, we aimed to test whether mutations at key sites have been detrimental to species-specific detection of P. pristis (Linnaeus, 1758) using the existing probe set. To test this hypothesis mitogenomes were assembled that were found to follow the typical pattern of vertebrate mitogenomic organization. Phylogenetic trees showed similar topologies and confirmed geographic mitochondrial variation in P. pristis. Mismatches for the published 12S species-specific probe set for P. pristis were identified that prevent amplification of positive control samples from Brazil. However, ddPCR detection of the positive control was possible using a newly designed species-specific probe set. This study highlights how geographical variation can severely impact the success of generally applying species-specific detection systems developed based on data from only one geographical region. The new mitogenomes and species-specific probe set developed here may also contribute to improving the potential to map and monitor these Critically Endangered species across the globe. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/639618v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1fb30fborg.highwire.dtl.DTLVardef@4cd3a8org.highwire.dtl.DTLVardef@1dbd985org.highwire.dtl.DTLVardef@a5d7d3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

ecology↗

bioRxiv2022

Nucleotide-free structures of Kif20A illuminate the atypical allostery in this mitotic kinesin-6

KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-EM microtubule-bound KIF20A structure that reveal the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that work to favor fast dissociation of ADP, particularly in contrast to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation thus highlight the role of extended insertions in shaping the motor mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker 4-times longer than kinesin-1 is required for the activity of this motor.

biochemistry↗