PDBsum entry 2h0b

Cell adhesion

PDB id: 2h0b

Contents

Protein chains

181 a.a. *

Ligands

GOL ×4

Metals

_CA ×4

Waters ×444

* Residue conservation analysis

PDB id:

2h0b

Name:

Cell adhesion

Title:

Crystal structure of the second lns/lg domain from neurexin 1 alpha

Structure:

Neurexin-1-alpha. Chain: a, b, c, d. Fragment: second lns/lg domain (residues 295-476). Synonym: neurexin i-alpha. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: nrxn1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.10Å R-factor: 0.186 R-free: 0.233

Authors:

L.R.Sheckler,L.Henry,S.Sugita,T.C.Sudhof,G.Rudenko

Key ref:

L.R.Sheckler et al. (2006). Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing. J Biol Chem, 281, 22896-22905. PubMed id: 16772286 DOI: 10.1074/jbc.M603464200

Date:

14-May-06 Release date: 20-Jun-06

Protein chains

Q28146  (NRX1A_BOVIN) -  Neurexin-1 from Bos taurus

Seq: 1530 a.a.

Struc: 181 a.a.

DOI no: 10.1074/jbc.M603464200

J Biol Chem 281:22896-22905 (2006)

PubMed id: 16772286

Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing.

L.R.Sheckler, L.Henry, S.Sugita, T.C.Südhof, G.Rudenko.

ABSTRACT

Neurexins mediate protein interactions at the synapse, playing an essential role in synaptic function. Extracellular domains of neurexins, and their fragments, bind a distinct profile of different proteins regulated by alternative splicing and Ca2+. The crystal structure of n1alpha_LNS#2 (the second LNS/LG domain of bovine neurexin 1alpha) reveals large structural differences compared with n1alpha_LNS#6 (or n1beta_LNS), the only other LNS/LG domain for which a structure has been determined. The differences overlap the so-called hyper-variable surface, the putative protein interaction surface that is reshaped as a result of alternative splicing. A Ca2+-binding site is revealed at the center of the hyper-variable surface next to splice insertion sites. Isothermal titration calorimetry indicates that the Ca2+-binding site in n1alpha_LNS#2 has low affinity (Kd approximately 400 microm). Ca2+ binding ceases to be measurable when an 8- or 15-residue splice insert is present at the splice site SS#2 indicating that alternative splicing can affect Ca2+-binding sites of neurexin LNS/LG domains. Our studies initiate a framework for the putative protein interaction sites of neurexin LNS/LG domains. This framework is essential to understand how incorporation of alternative splice inserts expands the information from a limited set of neurexin genes to produce a large array of synaptic adhesion molecules with potentially very different synaptic function.

Selected figure(s)

Figure 2.
FIGURE 2. Ribbon diagram of n1 _LNS#2. The -sandwich is shown in a face view (left) and side view (right). -Strands are depicted as yellow arrows, the single -helix is shown in magenta, and the Ca^2+ ion as a blue sphere. The N and C termini of the polypeptide chain are indicated with N and C, respectively.

Figure 4.
FIGURE 4. Ca^2^+-binding site in n1 _LNS#2. The SigmaA-weighted electron density 2m|F[o]| - D|F[c]| contoured at 1.2 and the atomic model are shown depicting the Ca^2+-binding site found at the hyper-variable surface of n1 LNS#2. Dotted lines indicate the interaction network between amino acid residues and solvent molecules chelating the Ca^2+ ion. The binding site in Mol2 is depicted (see Table 2).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 22896-22905) copyright 2006.

Figures were selected by an automated process.