Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase.
Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the catalytic alpha dimers of brain cytosolic platelet activating factor...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1797093451631689728 |
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| author | Tarricone, C Perrina, F Monzani, S Massimiliano, L Kim, M Derewenda, Z Knapp, S Tsai, L Musacchio, A |
| author_facet | Tarricone, C Perrina, F Monzani, S Massimiliano, L Kim, M Derewenda, Z Knapp, S Tsai, L Musacchio, A |
| author_sort | Tarricone, C |
| collection | OXFORD |
| description | Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH). The mechanism coupling the two diverse regulatory pathways remains unknown. We report the structure of LIS1 in complex with the alpha2/alpha2 PAF-AH homodimer. One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers. The same surface of LIS1 contains sites of mutations causing lissencephaly and overlaps with a putative dynein binding surface. Ndel1 competes with the alpha2/alpha2 homodimer for LIS1, but the interaction is complex and requires both the N- and C-terminal domains of LIS1. Our data suggest that the LIS1 molecule undergoes major conformational rearrangement when switching from a complex with the acetylhydrolase to the one with Ndel1. |
| first_indexed | 2024-03-07T04:00:36Z |
| format | Journal article |
| id | oxford-uuid:c4714176-27e5-4b12-b480-b019d5b81fa2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:00:36Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:c4714176-27e5-4b12-b480-b019d5b81fa22022-03-27T06:23:28ZCoupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4714176-27e5-4b12-b480-b019d5b81fa2EnglishSymplectic Elements at Oxford2004Tarricone, CPerrina, FMonzani, SMassimiliano, LKim, MDerewenda, ZKnapp, STsai, LMusacchio, AMutations in the LIS1 gene cause lissencephaly, a human neuronal migration disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the catalytic alpha dimers of brain cytosolic platelet activating factor acetylhydrolase (PAF-AH). The mechanism coupling the two diverse regulatory pathways remains unknown. We report the structure of LIS1 in complex with the alpha2/alpha2 PAF-AH homodimer. One LIS1 homodimer binds symmetrically to one alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta propellers. The same surface of LIS1 contains sites of mutations causing lissencephaly and overlaps with a putative dynein binding surface. Ndel1 competes with the alpha2/alpha2 homodimer for LIS1, but the interaction is complex and requires both the N- and C-terminal domains of LIS1. Our data suggest that the LIS1 molecule undergoes major conformational rearrangement when switching from a complex with the acetylhydrolase to the one with Ndel1. |
| spellingShingle | Tarricone, C Perrina, F Monzani, S Massimiliano, L Kim, M Derewenda, Z Knapp, S Tsai, L Musacchio, A Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title | Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title_full | Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title_fullStr | Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title_full_unstemmed | Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title_short | Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. |
| title_sort | coupling paf signaling to dynein regulation structure of lis1 in complex with paf acetylhydrolase |
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