PDBsum entry 1itf

Cytokine

PDB id: 1itf

Contents

Protein chain

165 a.a. *

* Residue conservation analysis

PDB id:

1itf

Name:

Cytokine

Title:

Interferon alpha-2a, nmr, 24 structures

Structure:

Interferon alpha-2a. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

24 models

Authors:

W.Klaus,B.Gsell,A.M.Labhardt,B.Wipf,H.Senn

Key ref:

W.Klaus et al. (1997). The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution. J Mol Biol, 274, 661-675. PubMed id: 9417943 DOI: 10.1006/jmbi.1997.1396

Date:

22-Aug-97 Release date: 03-Dec-97

Protein chain

P01563  (IFNA2_HUMAN) -  Interferon alpha-2 from Homo sapiens

Seq: 188 a.a.

Struc: 165 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1006/jmbi.1997.1396

J Mol Biol 274:661-675 (1997)

PubMed id: 9417943

The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution.

W.Klaus, B.Gsell, A.M.Labhardt, B.Wipf, H.Senn.

ABSTRACT

The solution structure of recombinant human interferon alpha-2a (Roferon-A) has been determined by multidimensional heteronuclear NMR spectroscopy. The calculations using simulated annealing produced a family of 24 convergent structures which satisfy the experimental restraints comprising 1541 NOE-derived inter-proton distances, 187 dihedral restraints, 66 pairs of hydrogen bond restraints, and six upper and lower limits for two disulfide bridges. The fractional labeling of methyl groups allowed their direct and unambiguous stereospecific assignment which proved to be essential for obtaining a high resolution of the structures. A best fit superposition of residues 10 to 47, 50 to 101 and 111 to 157 gives an rms deviation of 0.62 A for the backbone heavy atoms and 1.39 A for all heavy atoms of these segments. The dominant feature of the structure is a cluster of five alpha-helices, four of which are arranged to form a left-handed helix bundle with an up-up-down-down topology and two over-hand connections. The interpretation of heteronuclear 15N-¿1H¿ NOE data shows the co-existence of flexible regions within an otherwise rigid framework of the protein. Four stretches of pronounced flexibility can be located: Cys1-Ser8, Gly44-Ala50, Ile100-Lys112, and Ser160-Glu165. Among the structurally related four-helical bundle cytokines, the structure of IFN alpha-2a is most similar to that of human interferon alpha-2b and murine interferon-beta. From this structural information and mutagenesis data, areas on the surface of the protein are identified which seem to be important in receptor interactions.

Selected figure(s)

Figure 4.
Figure 4. Overlay of the side-chains of the well-defined amino acids of the final structures together with the polypeptide backbones (in yellow). The side-chains are colored according to residue type: Asp, Glu: red; Arg, Lys: dark blue; Ala, Ile, Leu, Phe, Val: cyan; Pro, Trp: green; Thr, Tyr, Ser: white. The flexible loops are clustered at the top of the structures.

Figure 5.
Figure 5. Overlay of the average NMR conformation of human interferon α-2a (in orange) and the X-ray structure of murine interferon-β (in cyan) [Senda et al 1995]. The α-helices are marked with labels A to E close to their N-terminal end. The Figure was prepared using the program Ribbons 2.0 [Carson 1991].

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 274, 661-675) copyright 1997.

Figures were selected by an automated process.