PDBsum entry 3cve

Signaling protein

PDB id: 3cve

Contents

Protein chains

68 a.a. *

61 a.a. *

Waters ×269

* Residue conservation analysis

PDB id:

3cve

Name:

Signaling protein

Title:

Crystal structure of the carboxy terminus of homer1

Structure:

Homer protein homolog 1. Chain: a, b, c, d. Fragment: coiled-coil region, unp residues 302-366. Synonym: psd-zip45, vasp/ena-related gene up-regulated during seizure and ltp. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: homer1, homer, vesl. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.75Å R-factor: 0.220 R-free: 0.289

Authors:

M.K.Hayashi,M.H.Stearns,V.Giannini,R.-M.Xu,C.Sala,Y.Hayashi

Key ref:

M.K.Hayashi et al. (2009). The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell, 137, 159-171. PubMed id: 19345194 DOI: 10.1016/j.cell.2009.01.050

Date:

18-Apr-08 Release date: 31-Mar-09

Protein chains

Q9Z214  (HOME1_RAT) -  Homer protein homolog 1 from Rattus norvegicus

Seq: 366 a.a.

Struc: 68 a.a.*

Protein chain

Q9Z214  (HOME1_RAT) -  Homer protein homolog 1 from Rattus norvegicus

Seq: 366 a.a.

Struc: 61 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1016/j.cell.2009.01.050

Cell 137:159-171 (2009)

PubMed id: 19345194

The postsynaptic density proteins Homer and Shank form a polymeric network structure.

M.K.Hayashi, C.Tang, C.Verpelli, R.Narayanan, M.H.Stearns, R.M.Xu, H.Li, C.Sala, Y.Hayashi.

ABSTRACT

The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we demonstrate that Homer and Shank, together, form a mesh-like matrix structure. Crystallographic analysis of this region revealed a pair of parallel dimeric coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving rise to the unique configuration of a pair of N-terminal EVH1 domains at each end of the coiled coil. In neurons, the tetramerization is required for structural integrity of the dendritic spines and recruitment of proteins to synapses. We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins.

Selected figure(s)

Figure 3.
Figure 3. Crystal Structure of the Homer Coiled-Coil Region
(A) Ribbon representation of the crystal structure of the C-terminal half of Homer1b coiled-coil region CC2. The four strands are marked A–D.
(B) A model of the whole structure of long form of Homer. The model is constructed from the structure of the Homer1CC2 domain (blue), EVH1 domain (red) (Irie et al., 2002), and coiled-coil probability prediction and protease degradation sites (Hayashi et al., 2006). The CC1 and a part of the CC2 domain, whose atomic structures are not known, are in light green and light blue, respectively. Regions likely to be disordered are shown in gray.
(C) Primary sequence of the crystallized fragment. 1B, rat Homer1b; 3A, human Homer3a. Orange, aliphatic residues (I, L, V); blue, acidic (D, E); green, basic (K, R); gray, residues not in crystals. Mutations made in dimeric Homer1b I332R/I337E are shown below. “abcdefg” denotes positions in the heptad of coiled coil.
(D) Distance between the A and the B strand or between the C and the D strand are measured and plotted against the number of residues.
(E) Helical wheel representation of the dimeric (top) and tetrameric (bottom) region of Homer1b. Residues start from K290 at g position. Residues that make knobs-into-holes interactions with residues on the other strands are shown in blue. Residues changed in the dimeric mutant (I332 and I337) are shown in red. Residues outside the dotted circles are located within the wide dimeric region.
(F) Example of intermolecular salt bridges formed between residues at the e (E295 and E302) and g (K290 and R297) positions within the dimeric region.
(G) Large amino acids occupying the a and d positions in the wide dimeric region, Q319 and F322.
(H) Interchain interactions in the tetrameric region. Residues at d positions (L329, K336, L343, L350) form the A-D and B-C interface, and those at e positions (L330, I337, R344, L351) form the A-C and B-D interface.
(I) Hydrophobic core formed by leucines at a positions (L326, L333, L340, L347).

Figure 7.
Figure 7. The Model of Interaction between Homer and Shank
(A) A model of high-order complex between Homer and Shank. Currently, the oligomeric status of Shank is not known.
(B) Overlay of the structural model of Homer (blue) on the PSD. The structure of mGluR1 (yellow) is modeled based on the structure of mGluR1 extracellular ligand binding domain (Kunishima et al., 2000) and the structure of rhodopsin (Palczewski et al., 2000). The structures of IP3R (red) (Sato et al., 2004), TRPC (green) (Mio et al., 2007), and dynamin (Mears et al., 2007) are taken from electron microscopy images. All structures are depicted to scale on an electron microscope image of a hippocampal CA1 spine with smooth endoplasmic reticulum, obtained and modified from Spacek and Harris (1997). Copyright 1997 by the Society for Neuroscience. The presynaptic terminal (Pre), postsynaptic terminal (Post), and endoplasmic reticulum (ER) are indicated. Scale bar, 0.1 μm.

The above figures are reprinted by permission from Cell Press: Cell (2009, 137, 159-171) copyright 2009.

Figures were selected by an automated process.