PDBsum entry 2rcj

Immune system

PDB id: 2rcj

Contents

Protein chains

(+ 4 more) 218 a.a.* *

(+ 4 more) 523 a.a.* *

104 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

2rcj

Name:

Immune system

Title:

Solution structure of human immunoglobulin m

Structure:

Iga1 light chain. Chain: a, b, e, f, i, j, m, n, q, r. Iga1 heavy chain. Chain: c, d, g, h, k, l, o, p, s, t. J chain. Chain: u

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: human immunoglobulin m was purified from the serum of a patient with waldenstrom's disease. A patient with waldenstrom's disease

Authors:

S.J.Perkins,A.S.Nealis,B.J.Sutton,A.Feinstein

Key ref:

S.J.Perkins et al. (1991). Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. J Mol Biol, 221, 1345-1366. PubMed id: 1942055 DOI: 10.1016/0022-2836(91)90937-2

Date:

20-Sep-07 Release date: 22-Jan-08

Protein chains

Q6PYX1  (Q6PYX1_HUMAN) -  Hepatitis B virus receptor binding protein (Fragment) from Homo sapiens

Seq: 348 a.a.

Struc: 218 a.a.*

Protein chains

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 523 a.a.*

Protein chain

No UniProt id for this chain

Struc: 104 a.a.

* PDB and UniProt seqs differ at 19 residue positions (black crosses)

reference

DOI no: 10.1016/0022-2836(91)90937-2

J Mol Biol 221:1345-1366 (1991)

PubMed id: 1942055

Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation.

S.J.Perkins, A.S.Nealis, B.J.Sutton, A.Feinstein.

ABSTRACT

The pentameric 71-domain structure of human and mouse immunoglobulin M (IgM) was investigated by synchrotron X-ray solution scattering and molecular graphics modelling. The radii of gyration RG of human IgM Quaife and its Fc5, IgM-S, Fab'2 and Fab fragments were determined as 12.2 nm, 6.1 nm, 6.1 nm, 4.9 nm and 2.9 nm in that order. The RG values were similar for mouse IgM P8 and its Fab'2 and Fab fragments, despite the presence of an additional carbohydrate site. The IgM scattering curves, to a nominal resolution of 5 nm, were compared with molecular graphics models based on published crystallographic alpha-carbon co-ordinates for the Fab and Fc structures of IgG. Good curve fits for Fab were obtained based on the crystal structure of Fab from IgG. A good curve fit was obtained for Fab'2, if the two Fab arms were positioned close together at their contact with the C mu 2 domains. The addition of the Fc fragment close to the C mu 2 domains of this Fab'2 model, to give a planar structure, accounted for the scattering curve of IgM-S. The Fc5 fragment was best modelled by a ring of five Fc monomers, constrained by packing considerations and disulphide bridge formation. A position for the J chain between two C mu 4 domains rather than at the centre of Fc5 was preferred. The intact IgM structure was best modelled using a planar arrangement of these Fab'2 and Fc5 models, with the side-to-side displacement of the Fab'2 arms in the plane of the IgM structure. All these models were consistent with hydrodynamic simulations of sedimentation data. The solution structure of IgM can therefore be reproduced quantitatively in terms of crystallographic structures for the fragments of IgG. Putative Clq binding sites have been identified on the C mu 3 domain. These would become accessible for interaction with Clq when the Fab'2 arms move out of the plane of the Fc5 disc in IgM, that is, a steric mechanism exposing pre-existing Clq sites. Comparison with a solution structure for Clq by neutron scattering shows that two or more of the six globular Clq heads in the hexameric head-and-stalk structure are readily able to make contacts with the putative Clq sites in the C mu 3 domains of free IgM if if the Clq arm-axis angle in solution is reduced from 40 degrees-45 degrees to 28 degrees. This could be the trigger for Cl activation.

Selected figure(s)

Figure 2.
Figure 2. A diagram of the j-sheet topology in the immunoglobulin fold of onstant domain. The 7 a-strands are labelled using the letters A to G in the Oxford convention (Williams & Barclay, 1988), and the letters X and Y in the Cambridge convention Beale & Feinstein, 1976). The intradomain disulphide bridge within each Ig fold (Fig. 1) connects he strands fx2 (B) and fy2 (F). The 6 bends are numbered bl to b6 in the Cambridge convention.

Figure 8.
Figure 8. Location f residues implicated in the ossible binding f Cl q to 1gM. (a) Thr posItions of His430. Aspi(:l~~ 432 and Pro436 (0) (see the t,ext) lie on the periphery of te Fc, disc. The relationship between 2 adjac-rnt Fc urlits of the pentamer shows how ys414 ( n ) is able to form disulphide bridges between them. Pairs ofcarbohydrat. sitt, rrsidur+ (A) at .4sn395 and Asn402 are shown for each Cp3 chain. (b) Face-on nd (c) side-o views of the structure seen in (a). t)ogethcr with a d-arm representation of Clq in contact with the rgion of His430. Asp/(:lu432 and I'ro436. In (b). (`I q is shown below the plane of t,he Fc Aructure. A Clq arm--axis angle of 28'' is required for c@irnal contacT hrtw-wn r' (`lq heads in the region of he shaded spheres and 2 adjacent Cl q sites on Fc indicated by 3 (a). It may hr seen that he (`1 q head must, in part at least, lie within te plane of the Fc, disc. The Debye model for I q is taken from Prrkins (1985). Figs 8 and 9 were created using INSIGHT TI (Biosym Inca., San Diego. (`4. I:.S.A.) c,n a Silicon ;raphics -CD%`lY~ \Vorkstation.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1991, 221, 1345-1366) copyright 1991.

Figures were selected by an automated process.