PDBsum entry 1a6p

Cell adhesion

PDB id: 1a6p

Contents

Protein chains

94 a.a. *

Waters ×81

* Residue conservation analysis

PDB id:

1a6p

Name:

Cell adhesion

Title:

Engineering of a misfolded form of cd2

Structure:

T-cell surface antigen cd2. Chain: a, b. Fragment: domain 1. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell: t-lymphocytes. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.08Å R-factor: 0.219 R-free: 0.296

Authors:

A.J.Murray,J.G.Head,J.J.Barker,R.L.Brady

Key ref:

A.J.Murray et al. (1998). Engineering an intertwined form of CD2 for stability and assembly. Nat Struct Biol, 5, 778-782. PubMed id: 9731771 DOI: 10.1038/1816

Date:

26-Feb-98 Release date: 17-Jun-98

Protein chains

P08921  (CD2_RAT) -  T-cell surface antigen CD2 from Rattus norvegicus

Seq: 344 a.a.

Struc: 94 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/1816

Nat Struct Biol 5:778-782 (1998)

PubMed id: 9731771

Engineering an intertwined form of CD2 for stability and assembly.

A.J.Murray, J.G.Head, J.J.Barker, R.L.Brady.

ABSTRACT

The amino-terminal domain of CD2 has the remarkable ability to fold in two ways: either as a monomer or as an intertwined, metastable dimer. Here we show that it is possible to differentially stabilize either fold by engineering the CD2 sequence, mimicking random mutagenesis events that could occur during molecular evolution. Crystal structures of a hinge-deletion mutant, which is stable as an intertwined dimer, reveal domain rotations that enable the protein to further assemble to a tetramer. These results demonstrate that a variety of folds can be adopted by a single polypeptide sequence, and provide guidance for the design of proteins capable of further assembly.

Selected figure(s)

Figure 3.
Figure 3. Stereo C traces depicting the crystal structures of a, the wild type intertwined dimer, with the enclosed hydrophilic interface, and b, in a similar orientation, the 46 47 deletion mutant intertwined dimer in the P4[3] crystal form (forms I and II). The hydrophilic interface is now in an 'exposed' conformation. When crystallized under high-salt conditions (crystal form III) c, this same structure is also observed, but now a tetramer is formed in which a second intertwined dimer binds with both hydrophilic interfaces interlocked to form a central, extended -barrel. The spheres identify the location of equivalent residues (position 49) central to each polypeptide chain, illustrating their close proximity in the tetramer and hence the feasibility of further exchange of polypeptide chains in this region to form a fully intertwined tetramer.

Figure 4.
Figure 4. Stereo view of electron density (3F[o] - 2F[c] coefficients, contoured at 1 ) from the hinge region residues in the P4[3], type I, crystal form of the 46 47 deletion mutant intertwined dimer. The deletion site is adjacent to the proline in the center of the figure.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1998, 5, 778-782) copyright 1998.

Figures were selected by an automated process.