PDBsum entry 1dg3

Signaling protein

PDB id: 1dg3

Contents

Protein chain

540 a.a. *

Waters ×341

* Residue conservation analysis

PDB id:

1dg3

Name:

Signaling protein

Title:

Structure of human guanylate binding protein-1 in nucleotide free form

Structure:

Protein (interferon-induced guanylate-binding protein 1). Chain: a. Fragment: full length protein. Synonym: guanine nucleotide- binding protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

1.80Å R-factor: 0.242 R-free: 0.276

Authors:

B.Prakash,G.J.K.Praefcke,L.Renault,A.Wittinghofer,C.Herrmann

Key ref:

B.Prakash et al. (2000). Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature, 403, 567-571. PubMed id: 10676968 DOI: 10.1038/35000617

Date:

23-Nov-99 Release date: 11-Oct-00

Protein chain

P32455  (GBP1_HUMAN) -  Guanylate-binding protein 1 from Homo sapiens

Seq: 592 a.a.

Struc: 540 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.3.6.1.- - ?????
• Enzyme class 3: E.C.3.6.5.- - ?????

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.

DOI no: 10.1038/35000617

Nature 403:567-571 (2000)

PubMed id: 10676968

Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins.

B.Prakash, G.J.Praefcke, L.Renault, A.Wittinghofer, C.Herrmann.

ABSTRACT

Interferon-gamma is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2. These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity and an antiviral effect. Here we have determined the crystal structure of full-length human GBP1 to 1.8 A resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity.

Selected figure(s)

Figure 2.
Figure 2: Comparison of hGBP1 and Ras structures. a, Superimposition of the LG domain of hGBP1 with the G domain of Ras in complex with GDP(PDB accession no. 1Q21) as a stereo view. N-terminal residues 1-36 of hGBP1 up to 1 have been omitted for clarity. The colour code is as in Fig. 1; Ras is in cyan. b, Putative location of nucleotide-binding site in hGBP1. The regions of hGBP1 potentially involved in binding the guanine nucleotide are shown as obtained from a structural superimposition of RasGDP (in cyan) with the corresponding regions in hGBP1 (purple), highlighting functionally important residues necessary for binding and conformational change as balls or in ball-and-stick. Whereas Gly 60^ras overlays very well with Gly 100^hGBP1, residues D119/D184 and T35/T75 do not.

Figure 3.
Figure 3: Interaction of the C-terminal helix motif alpha-12/13 with the helical and the LG domains. The electrostatic surface potential shows that the highly charged regions of the helical and LG domains are masked by an 12/13 motif, as indicated in the lower panel by showing 12/ 13 in worm representation.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 403, 567-571) copyright 2000.

Figures were selected by an automated process.