1VYH

PAF-AH Holoenzyme: Lis1/Alfa2

Summary for 1VYH

• Entry DOI: 10.2210/pdb1vyh/pdb
• Related: 1FXW
• Descriptor: PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IB BETA SUBUNIT, PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IB ALPHA SUBUNIT (2 entities in total)
• Functional Keywords: lissencephaly, acetylhydrolase, platelet activacting factor, regulator of cytoplasmic dynein, hydrolase, cell division, mitosis, neurogenesis, cytoskeleton
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytoskeleton: P63005
• Total number of polymer chains: 20
• Total formula weight: 723863.97

Authors

Tarricone, C.,Perrina, F.,Monzani, S.,Massimiliano, L.,Knapp, S.,Tsai, L.-H.,Derewenda, Z.S.,Musacchio, A. (deposition date: 2004-04-30, release date: 2005-05-26, Last modification date: 2023-12-13)

Primary citation

Tarricone, C.,Perrina, F.,Monzani, S.,Massimiliano, L.,Kim, M.H.,Derewenda, Z.S.,Knapp, S.,Tsai, L.-H.,Musacchio, A.
Coupling Paf Signaling to Dynein Regulation: Structure of Lis1 in Complex with Paf-Acetylhydrolase.
Neuron, 44:809-, 2004

PubMed Abstract: 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.

PubMed: 15572112
DOI: 10.1016/J.NEURON.2004.11.019

Experimental method

X-RAY DIFFRACTION (3.4 Å)