%0 Journal Article %A Hackney, David %A Baek, Nahyeon %A Snyder, Avin C. %D 2009 %T Half-site inhibition of dimeric kinesin head domains by monomeric tail domains. %U https://kilthub.cmu.edu/articles/journal_contribution/Half-site_inhibition_of_dimeric_kinesin_head_domains_by_monomeric_tail_domains_/6099404 %R 10.1184/R1/6099404.v1 %2 http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19320433/ %K Animals %K Binding Sites %K Dimerization %K Drosophila Proteins %K Kinesin %K Models %K Molecular %K Peptide Fragments %K Protein Binding %K Protein Conformation %K Protein Folding %K Protein Structure %K Tertiary %X

The two heavy chains of kinesin-1 are dimerized through extensive coiled coil regions and fold into an inactive conformation through interaction of the C-terminal tail domains with the N-terminal motor (head) domains. Although this potentially allows a dimer of tail domains to interact symmetrically with a dimer of head domains, we report here that only one of the two available monomeric tail peptides is sufficient for tight binding and inhibition of a dimer of head domains. With a dimeric tail construct, the other tail peptide does not make tight contact with the head dimer and can bind a second head dimer to form a complex containing one tail dimer and two head dimers. The IAK domain and neighboring positively charged region of the tail is sufficient for tight half-site interaction with a dimer of heads. The interaction of tails with monomeric heads is weak, but a head dimer produced by the dimerization of the neck coil is not required because an artificial dimer of head domains also binds monomeric tail peptides with half-site stoichiometry in the complete absence of the native neck coil. The binding of tail peptides to head dimers is fast and readily reversible as determined by FRET between mant-ADP bound to the head dimer and a tail labeled with GFP. The association and dissociation rates are 81 microM(-1) s(-1) and 32 s(-1), respectively. This half-site interaction suggests that the second tail peptide in a folded kinesin-1 might be available to bind other molecules while kinesin-1 remained folded.

%I Carnegie Mellon University