Matches in SemOpenAlex for { <https://semopenalex.org/work/W4319080908> ?p ?o ?g. }
- W4319080908 abstract "Abstract Mutations in the Kinesin-3 motor KIF1A, a microtubule (MT)-associated motor protein, cause devastating neurodevelopmental and neurodegenerative diseases termed KIF1A-associated neurological disorders (KAND). While the mechanism of KIF1A is increasingly understood, high resolution (<4 Å) structural information of KIF1A-MT complexes is lacking. Here, we present 2.7-3.4 Å resolution structures of dimeric MT-bound wild-type (WT) KIF1A and the pathogenic P305L mutant as a function of the nucleotide state. Our structures reveal that 1) the KIF1A dimer binds MTs in one- and two-heads-bound states, 2) that both MT-bound heads assume distinct conformations with tight inter-head connection, 3) the position and conformation of the class-specific loop 12 (the K-loop), and 4) that the P305L mutation causes structural changes in the K-loop that result in a weakly MT-bound state. Motivated by our structural insights, we performed structure-function studies that reveal that both the K-loop and head-head coordination are major determinants of KIF1A’s superprocessive motility. Our work provides key insights into the mechanism of KIF1A and provides near-atomic structures of WT and mutant KIF1A for future structure-guided drug-design approaches to treat KAND." @default.
- W4319080908 created "2023-02-04" @default.
- W4319080908 creator A5017071578 @default.
- W4319080908 creator A5028972631 @default.
- W4319080908 creator A5029972358 @default.
- W4319080908 creator A5062012877 @default.
- W4319080908 creator A5087227678 @default.
- W4319080908 date "2023-02-03" @default.
- W4319080908 modified "2023-09-27" @default.
- W4319080908 title "High-Resolution structures of microtubule-bound KIF1A and its pathogenic variant P305L" @default.
- W4319080908 cites W1534597181 @default.
- W4319080908 cites W1595347157 @default.
- W4319080908 cites W1882922344 @default.
- W4319080908 cites W1974160934 @default.
- W4319080908 cites W1985145180 @default.
- W4319080908 cites W1986498027 @default.
- W4319080908 cites W1987390280 @default.
- W4319080908 cites W1989655238 @default.
- W4319080908 cites W1993552170 @default.
- W4319080908 cites W2003017523 @default.
- W4319080908 cites W2005128877 @default.
- W4319080908 cites W2012855723 @default.
- W4319080908 cites W2029120000 @default.
- W4319080908 cites W2032146255 @default.
- W4319080908 cites W2033759150 @default.
- W4319080908 cites W2043704625 @default.
- W4319080908 cites W2050270347 @default.
- W4319080908 cites W2056350584 @default.
- W4319080908 cites W2056648746 @default.
- W4319080908 cites W2057733928 @default.
- W4319080908 cites W2061092318 @default.
- W4319080908 cites W2062700329 @default.
- W4319080908 cites W2062714245 @default.
- W4319080908 cites W2066874327 @default.
- W4319080908 cites W2076449818 @default.
- W4319080908 cites W2079583250 @default.
- W4319080908 cites W2080441213 @default.
- W4319080908 cites W2084283552 @default.
- W4319080908 cites W2087838338 @default.
- W4319080908 cites W2093797951 @default.
- W4319080908 cites W2097936604 @default.
- W4319080908 cites W2106906854 @default.
- W4319080908 cites W2109639149 @default.
- W4319080908 cites W2110213040 @default.
- W4319080908 cites W2111661564 @default.
- W4319080908 cites W2122755030 @default.
- W4319080908 cites W2132629607 @default.
- W4319080908 cites W2133573698 @default.
- W4319080908 cites W2143546222 @default.
- W4319080908 cites W2144081223 @default.
- W4319080908 cites W2148674149 @default.
- W4319080908 cites W2153492153 @default.
- W4319080908 cites W2156044796 @default.
- W4319080908 cites W2165041848 @default.
- W4319080908 cites W2166088282 @default.
- W4319080908 cites W2168166944 @default.
- W4319080908 cites W2180229411 @default.
- W4319080908 cites W2235805225 @default.
- W4319080908 cites W2294227584 @default.
- W4319080908 cites W2312551248 @default.
- W4319080908 cites W2316491903 @default.
- W4319080908 cites W2345334325 @default.
- W4319080908 cites W2393757600 @default.
- W4319080908 cites W2411563451 @default.
- W4319080908 cites W2472301418 @default.
- W4319080908 cites W2517363650 @default.
- W4319080908 cites W2556772084 @default.
- W4319080908 cites W2599437710 @default.
- W4319080908 cites W2600841728 @default.
- W4319080908 cites W2611412286 @default.
- W4319080908 cites W2734356283 @default.
- W4319080908 cites W2748092720 @default.
- W4319080908 cites W2759165639 @default.
- W4319080908 cites W2764154652 @default.
- W4319080908 cites W2766903323 @default.
- W4319080908 cites W2791354025 @default.
- W4319080908 cites W2795033945 @default.
- W4319080908 cites W2801129497 @default.
- W4319080908 cites W2808041165 @default.
- W4319080908 cites W2890294352 @default.
- W4319080908 cites W2895355140 @default.
- W4319080908 cites W2898912519 @default.
- W4319080908 cites W2899714098 @default.
- W4319080908 cites W2900466955 @default.
- W4319080908 cites W2907624470 @default.
- W4319080908 cites W2909290620 @default.
- W4319080908 cites W2913616282 @default.
- W4319080908 cites W2950967305 @default.
- W4319080908 cites W2965835491 @default.
- W4319080908 cites W2970462530 @default.
- W4319080908 cites W2971060309 @default.
- W4319080908 cites W2971491823 @default.
- W4319080908 cites W2972124904 @default.
- W4319080908 cites W2985181896 @default.
- W4319080908 cites W2992325975 @default.
- W4319080908 cites W2993280571 @default.
- W4319080908 cites W3004450961 @default.
- W4319080908 cites W3006717921 @default.
- W4319080908 cites W3006848357 @default.
- W4319080908 cites W3123673969 @default.