PDBsum entry 2v70

Structural protein

PDB id: 2v70

Contents

Protein chains

210 a.a. *

Ligands

NAG ×4

* Residue conservation analysis

PDB id:

2v70

Name:

Structural protein

Title:

Third lrr domain of human slit2

Structure:

Slit homolog 2 protein n-product. Chain: a, b, c, d. Fragment: third lrr domain, residues 504-714. Synonym: slit-2. Engineered: yes. Other_details: glycosylation on n623

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293.

Resolution:

3.01Å R-factor: 0.225 R-free: 0.271

Authors:

C.Morlot,S.Cusack,A.A.Mccarthy

Key ref:

C.Morlot et al. (2007). Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3. Acta Crystallogr D Biol Crystallogr, 63, 961-968. PubMed id: 17704564 DOI: 10.1107/S0907444907035470

Date:

24-Jul-07 Release date: 28-Aug-07

Protein chains

O94813  (SLIT2_HUMAN) -  Slit homolog 2 protein from Homo sapiens

Seq: 1529 a.a.

Struc: 210 a.a.

DOI no: 10.1107/S0907444907035470

Acta Crystallogr D Biol Crystallogr 63:961-968 (2007)

PubMed id: 17704564

Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3.

C.Morlot, W.Hemrika, R.A.Romijn, P.Gros, S.Cusack, A.A.McCarthy.

ABSTRACT

Slit2 and Roundabout 1 (Robo1) provide a key ligand-receptor interaction for the navigation of commissural neurons during the development of the central nervous system. Slit2 is a large multidomain protein containing an unusual domain organization of four tandem leucine-rich repeat (LRR) domains at its N-terminus. These domains are well known to mediate protein-protein interactions; indeed, the Robo1-binding region has been mapped to the concave face of the second LRR domain. It has also been shown that the fourth LRR domain may mediate Slit dimerization and that both the first and second domains can bind heparin. Thus, while roles have been ascribed for three of the LRR domains, there is still no known role for the third domain. Each of the four LRR domains from human Slit2 have now been successfully expressed in milligram quantities using expression in mammalian cells. Here, the crystallization of the second and third LRR domains and the structure of the third LRR domain are presented. This is the first structure of an LRR domain from human Slit2, which has an extra repeat compared with the Drosophila homologue. It is proposed that a highly conserved patch of surface residues on the concave face may mediate any protein-protein interactions involving this LRR domain, a result that will be useful in guiding further studies on Slit2.

Selected figure(s)

Figure 2.
Figure 2 Structure of Slit2 LRR domains. The N- and C-terminal capping domains are shown in purple and blue, respectively, and the LRR repeats are coloured orange. The disulfide bridges are drawn in yellow ball-and-stick representation and the N-acetylglucosamine is drawn in green stick representation. (a, b) Ribbon diagram of human Slit2 D3 in two orthogonal orientations. (c) Ribbon diagram of Drosophila Slit D3.

Figure 4.
Figure 4 The sequence conservation of surface residues was mapped onto Slit2 D3 and is indicated with a colour gradient from dark green (most conserved) to white (most divergent) in two orientations. (a) Concave face in an orientation identical to Fig. 2-. (b) Convex face showing the N-acetylglucosamine. The sequence conservation was mapped onto the surface with ConSurf (Landau et al., 2005[Landau, M., Mayrose, I., Rosenberg, Y., Glaser, F., Martz, E., Pupko, T. & Ben-Tal, N. (2005). Nucleic Acids Res. 33, W299-W302.]).

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 961-968) copyright 2007.

Figures were selected by an automated process.