PDBsum entry 3cu7

Immune system

PDB id

3cu7

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Contents

			Protein chains

					1625 a.a. *


					1481 a.a. *

			Ligands

					NAG-NAG ×2


					NAG ×2

			Metals

					_CD ×9

* Residue conservation analysis

PDB id:

3cu7

Links

Name:

Immune system

Title:

Human complement component 5

Structure:

Complement c5. Chain: a, b. Synonym: c3 and pzp-like alpha-2-macroglobulin domain-containing protein 4

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood

Resolution:

3.11Å

R-factor:

0.238

R-free:

0.281

Authors:

F.Fredslund,G.R.Andersen

Key ref:

F.Fredslund et al. (2008). Structure of and influence of a tick complement inhibitor on human complement component 5. Nat Immunol, 9, 753-760. PubMed id: 18536718 DOI: 10.1038/ni.1625

Date:

16-Apr-08

Release date:

10-Jun-08

PROCHECK

	Headers

	References

Protein chain

P01031 (CO5_HUMAN) - Complement C5 from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					1676 a.a. 1625 a.a.*

Protein chain

P01031 (CO5_HUMAN) - Complement C5 from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					1676 a.a. 1481 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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

DOI no: 10.1038/ni.1625	Nat Immunol 9:753-760 (2008)
PubMed id: 18536718

Structure of and influence of a tick complement inhibitor on human complement component 5.
F.Fredslund, N.S.Laursen, P.Roversi, L.Jenner, C.L.Oliveira, J.S.Pedersen, M.A.Nunn, S.M.Lea, R.Discipio, L.Sottrup-Jensen, G.R.Andersen.

ABSTRACT

To provide insight into the structural and functional properties of human complement component 5 (C5), we determined its crystal structure at a resolution of 3.1 A. The core of C5 adopted a structure resembling that of C3, with the domain arrangement at the position corresponding to the C3 thioester being very well conserved. However, in contrast to C3, the convertase cleavage site in C5 was ordered and the C345C domain flexibly attached to the core of C5. Binding of the tick C5 inhibitor OmCI to C5 resulted in stabilization of the global conformation of C5 but did not block the convertase cleavage site. The structure of C5 may render possible a structure-based approach for the design of new selective complement inhibitors.

Selected figure(s)



	Figure 2. (a) Packing of the MG8 (green) and the C5d (gray) domains in C5 around Ser1007 and Ala1010. (b) The region in a at the thioester (TE) formed by Cys1009 and Gln1012 in bovine C3 (orange) superimposed onto the C5d domain of C5 (green and gray, as in a). (c) The thioester formed by Cys838 and Gln841 in TEP (light blue) and in C5 (green and gray). In b and c, the catalytic histidine residues 1125 and 951 are in the foreground.

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21352072

C.Walgaard, B.C.Jacobs, and P.A.van Doorn (2011).
Emerging drugs for Guillain-Barré syndrome.

Expert Opin Emerg Drugs, 16, 105-120.

21217642

N.S.Laursen, K.R.Andersen, I.Braren, E.Spillner, L.Sottrup-Jensen, and G.R.Andersen (2011).
Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex.

EMBO J, 30, 606-616.

PDB codes:

3prx 3pvm

20545943

J.Bestebroer, P.C.Aerts, S.H.Rooijakkers, M.K.Pandey, J.Köhl, J.A.van Strijp, and C.J.de Haas (2010).
Functional basis for complement evasion by staphylococcal superantigen-like 7.

Cell Microbiol, 12, 1506-1516.

20666732

K.Li, J.Gor, and S.J.Perkins (2010).
Self-association and domain rearrangements between complement C3 and C3u provide insight into the activation mechanism of C3.

Biochem J, 431, 63-72.

20133685

N.S.Laursen, N.Gordon, S.Hermans, N.Lorenz, N.Jackson, B.Wines, E.Spillner, J.B.Christensen, M.Jensen, F.Fredslund, M.Bjerre, L.Sottrup-Jensen, J.D.Fraser, and G.R.Andersen (2010).
Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.

Proc Natl Acad Sci U S A, 107, 3681-3686.

PDB codes:

3kls 3km9

20017116

R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.

J Mol Recognit, 23, 1.

20124699

W.J.Cook, N.Galakatos, W.C.Boyar, R.L.Walter, and S.E.Ealick (2010).
Structure of human desArg-C5a.

Acta Crystallogr D Biol Crystallogr, 66, 190-197.

PDB codes:

3hqa 3hqb

19194881

J.Soltys, L.L.Kusner, A.Young, C.Richmonds, D.Hatala, B.Gong, V.Shanmugavel, and H.J.Kaminski (2009).
Novel complement inhibitor limits severity of experimentally myasthenia gravis.

Ann Neurol, 65, 67-75.

19769446

K.Kaida, and S.Kusunoki (2009).
Guillain-Barré syndrome: update on immunobiology and treatment.

Expert Rev Neurother, 9, 1307-1319.

19419965

M.M.Phelan, C.T.Thai, D.C.Soares, R.T.Ogata, P.N.Barlow, and J.Bramham (2009).
Solution Structure of Factor I-like Modules from Complement C7 Reveals a Pair of Follistatin Domains in Compact Pseudosymmetric Arrangement.

J Biol Chem, 284, 19637-19649.

PDB code:

2wcy

19503103

S.H.Rooijakkers, J.Wu, M.Ruyken, R.van Domselaar, K.L.Planken, A.Tzekou, D.Ricklin, J.D.Lambris, B.J.Janssen, J.A.van Strijp, and P.Gros (2009).
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.

Nat Immunol, 10, 721-727.

PDB code:

2win

19368894

V.Krishnan, K.Ponnuraj, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2009).
The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb.

Structure, 17, 611-619.

PDB code:

3frp

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.