Structural basis of katanin function at microtubule minus end

Katanin plays a cru cial role in se vere hu man dis eases such as tauophaties or microcephaly [1-2]. It is a micro tu bulesev er ing en zyme that has the unique ca pac ity to catalyse the re moval of tubulin dimers from the in te rior of the microtubule lat tice and thereby cut microtubules (MT) into short frag ments. It is nec es sary for mei otic spin dle as sem bly, de ter mi na tion of mi totic spin dle length, sev er ing at microtubule cross overs, and cell mo til ity [3-4]. Katanin is known for de cades; how ever, struc tural in for ma tion is miss ing and the role of in ter ac tion part ners in the reg u la tion of katanin func tion is not fully un der stood. Here we per formed a de tailed bio phys i cal, struc tural and func tional char ac ter iza tion of katanin alone and in com plex with two bind ing part ners, ASPM (ab nor mal spin dle-like microcephaly-as so ci ated pro tein) and CAMSAP (calmodulin-reg u lated spectrin-as so ci ated pro tein). We iden ti fied min i mal re gions of CAMSAP and ASPM nec es sary and suf fi cient for the in ter ac tion with katanin. We char ac ter ized the com plexes bio physi cally us ing mainly sed i men ta tion ve loc ity an a lyt i cal centrifugation and solved the crys tal struc tures of katanin, and the katanin/CAMSAP, katanin/ASPM com plexes. Our work re vealed that CAMSAP and ASPM com pete for the same bind ing site on katanin and func tional anal y sis showed that katanin/ASPM and katanin/CAMSAP form MT mi nus-end bind ing complexes, that play major roles in regulating MT dynamics.