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1vyh
From Proteopedia
PAF-AH HOLOENZYME: LIS1/ALFA2
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.
Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase., Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim MH, Derewenda ZS, Knapp S, Tsai LH, Musacchio A, Neuron. 2004 Dec 2;44(5):809-21. PMID:15572112
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1VYH is a 20 chains structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
- Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim MH, Derewenda ZS, Knapp S, Tsai LH, Musacchio A. Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. Neuron. 2004 Dec 2;44(5):809-21. PMID:15572112 doi:10.1016/j.neuron.2004.11.019
Page seeded by OCA on Mon Feb 16 23:43:12 2009
Categories: 1-alkyl-2-acetylglycerophosphocholine esterase | Homo sapiens | Mus musculus | Derewenda, Z S. | Knapp, S. | Massimiliano, L. | Monzani, S. | Musacchio, A. | Perrina, F. | Tarricone, C. | Tsai, L H. | Acetylhydrolase | Cell division | Cytoskeleton | Hydrolase | Lissencephaly | Mitosis | Neurogenesis | Platelet activacting factor | Regulator of cytoplasmic dynein

