PDBsum entry 1nwv

Biosynthetic protein

PDB id: 1nwv

Contents

Protein chain

129 a.a. *

* Residue conservation analysis

PDB id:

1nwv

Name:

Biosynthetic protein

Title:

Solution structure of a functionally active component of decay accelerating factor

Structure:

Complement decay-accelerating factor. Chain: a. Synonym: cd55 antigen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: daf or cr or cd55. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

NMR struc:

42 models

Authors:

S.Uhrinova,F.Lin,G.Ball,K.Bromek,D.Uhrin,M.E.Medof,P.N.Barlow

Key ref:

S.Uhrinova et al. (2003). Solution structure of a functionally active fragment of decay-accelerating factor. Proc Natl Acad Sci U S A, 100, 4718-4723. PubMed id: 12672958 DOI: 10.1073/pnas.0730844100

Date:

07-Feb-03 Release date: 22-Apr-03

Protein chain

P08174  (DAF_HUMAN) -  Complement decay-accelerating factor from Homo sapiens

Seq: 381 a.a.

Struc: 129 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1073/pnas.0730844100

Proc Natl Acad Sci U S A 100:4718-4723 (2003)

PubMed id: 12672958

Solution structure of a functionally active fragment of decay-accelerating factor.

S.Uhrinova, F.Lin, G.Ball, K.Bromek, D.Uhrin, M.E.Medof, P.N.Barlow.

ABSTRACT

The second and third modules of human decay accelerating factor (DAF) are necessary and sufficient to accelerate decay of the classical pathway (CP) convertase of complement. No structure of a mammalian protein with decay-accelerating activity has been available to date. We therefore determined the solution structure of DAF modules 2 and 3 (DAF approximately 2,3). Structure-guided analysis of 24 mutants identified likely contact points between DAF and the CP convertase. Three (R96, R69, and a residue in the vicinity of L171) lie on DAF approximately 2,3's concave face. A fourth, consisting of K127 and nearby R100, is on the opposite face. Regions of module 3 remote from the semiflexible 2-3 interface seem not to be involved in binding to the CP convertase. DAF thus seems to occupy a groove on the CP convertase such that both faces of DAF close to the 2-3 junction (including a positively charged region that encircles the protein at this point) interact simultaneously. Alternative pathway convertase interactions with DAF require additional regions of CCP 3 lying away from the 2-3 interface, consistent with the established additional requirement of module 4 for alternative pathway regulation.

Selected figure(s)

Figure 2.
Fig 2. The solution structure of DAF 2,3. (a) Overlay (backbone trace) of 42 lowest energy structures on selected CCP-3 C s of structure closest to the mean. (b) As in a but structures overlaid on selected C s of CCP-2. (c) MOLSCRIPT trace (showing Cys and Trp) of structure with intermodular angles closest to average; hv, hypervariable loop; loops, turns, and bulges are labeled with aa numbers; strands are annotated as in Fig. 1.

Figure 3.
Fig 3. Intermodular angles in DAF 2,3. (a) Distribution of tilt (filled), twist (gray), and skew (open) angles for the 42 lowest energy structures [definition of angles (34) summarized in Inset]. (b) Angles plotted by using polar coordinates; each wedge summarizes mean ± SD for the angle indicated.

Figures were selected by an automated process.