PDBsum entry 1vyh

Hydrolase

PDB id: 1vyh

Contents

Protein chains

(+ 4 more) 218 a.a. *

(+ 4 more) 310 a.a. *

* Residue conservation analysis

PDB id:

1vyh

Name:

Hydrolase

Title:

Paf-ah holoenzyme: lis1/alfa2

Structure:

Platelet-activating factor acetylhydrolase ib beta subunit. Chain: a, b, e, f, i, j, m, n, q, r. Synonym: platelet-activating factor acetylhydrolase, paf acetylhydrolase 30 kda subunit, paf-ah 30 kda subunit, paf-ah beta subunit, pafah beta subunit. Engineered: yes. Platelet-activating factor acetylhydrolase ib alpha subunit. Chain: c, d, g, h, k, l, o, p, s, t.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Mus musculus. Mouse. Organism_taxid: 10090. Organ: brain.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.40Å R-factor: 0.265 R-free: 0.307

Authors:

C.Tarricone,F.Perrina,S.Monzani,L.Massimiliano,S.Knapp,L.-H.Tsai, Z.S.Derewenda,A.Musacchio

Key ref:

C.Tarricone et al. (2004). Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. Neuron, 44, 809-821. PubMed id: 15572112 DOI: 10.1016/j.neuron.2004.11.019

Date:

30-Apr-04 Release date: 26-May-05

Protein chains

P68402  (PA1B2_HUMAN) -  Platelet-activating factor acetylhydrolase IB subunit alpha2 from Homo sapiens

Seq: 229 a.a.

Struc: 218 a.a.

Protein chains

P63005  (LIS1_MOUSE) -  Platelet-activating factor acetylhydrolase IB subunit beta from Mus musculus

Seq: 410 a.a.

Struc: 310 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B, E, F, I, J, M, N, Q, R: E.C.3.1.1.47 - 1-alkyl-2-acetylglycerophosphocholine esterase.
• Reaction: a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl- sn-glycero-3-phosphocholine + acetate + H⁺
• Enzyme class 2: Chains C, D, G, H, K, L, O, P, S, T: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/j.neuron.2004.11.019

Neuron 44:809-821 (2004)

PubMed id: 15572112

Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase.

C.Tarricone, F.Perrina, S.Monzani, L.Massimiliano, M.H.Kim, Z.S.Derewenda, S.Knapp, L.H.Tsai, A.Musacchio.

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.

Selected figure(s)

Figure 3.
Figure 3. Comparison of LIS1/PAF-AH and G[αβγ](A) Ribbon diagram of the G[αβγ] trimer based on PDB coordinates 1GP2 (Wall et al., 1995). G[α] is yellow and is subdivided in the Ras-like domain (light yellow) and in the helical domain (dark yellow). G[β] is cyan and G[γ] is green. The G[α]-G[βγ] interaction involves the N-terminal helix and the switch I and switch II regions of G[α] (red). The G[β] subunit uses the top surface of the β propeller, where the outer βD strand connects to the inner βA strand of the next blade to bind G[α]. The top surface is preferentially used for ligand recognition by propeller-like structures (Smith et al., 1999).(B) A LIS1/PAF-AH hemitetramer is shown. The α[2] subunit has the same orientation of the G[α] subunit shown in (A). The orientation of the β subunits is unrelated, although also in this case the top surface of the propeller is used for binding.

Figure 7.
Figure 7. A Model for LIS1/Ndel1 and Its Interacton with DyneinTo reconcile the two-fold symmetry of LIS1 with that of Ndel1, we postulated that Ndel1 forms an antiparallel coiled coil. The α4 helices of N-LIS1 interact with Ndel1, and so does the β propeller region. The two β propellers of LIS1 bind dynein at distinct sites in the first AAA module and in the stem (Tai et al., 2002). Because the dynein heavy chain that contributes a sizable fraction of the stem is a dimer (Holzbaur and Vallee, 1994), the overall assembly may be duplicated (represented by the gray, dashed drawing).

The above figures are reprinted by permission from Cell Press: Neuron (2004, 44, 809-821) copyright 2004.

Figures were selected by an automated process.