PDBsum entry 4lve

Immunoglobulin

PDB id: 4lve

Contents

Protein chains

114 a.a. *

Waters ×201

* Residue conservation analysis

PDB id:

4lve

Name:

Immunoglobulin

Title:

Len k30t mutant: a domain flip as a result of a single amino acid substitution

Structure:

Len. Chain: a, b. Engineered: yes. Mutation: yes. Other_details: kappa-iv light chain dimer

Source:

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

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.190 R-free: 0.267

Authors:

M.Schiffer,P.R.Pokkuluri

Key ref:

P.R.Pokkuluri et al. (1998). A domain flip as a result of a single amino-acid substitution. Structure, 6, 1067-1073. PubMed id: 9739086 DOI: 10.1016/S0969-2126(98)00107-5

Date:

12-May-98 Release date: 18-May-99

Protein chains

P06312  (KV401_HUMAN) -  Immunoglobulin kappa variable 4-1 from Homo sapiens

Seq: 121 a.a.

Struc: 114 a.a.*

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

DOI no: 10.1016/S0969-2126(98)00107-5

Structure 6:1067-1073 (1998)

PubMed id: 9739086

A domain flip as a result of a single amino-acid substitution.

P.R.Pokkuluri, D.B.Huang, R.Raffen, X.Cai, G.Johnson, P.W.Stevens, F.J.Stevens, M.Schiffer.

ABSTRACT

BACKGROUND: The self-assembly properties of beta domains are important features of diverse classes of proteins that include cell-adhesion molecules, surface receptors and the immunoglobulin superfamily. Immunoglobulin light-chain variable domains are well suited to the study of structural factors that determine dimerization, including how residues at the interface influence the preferred dimer arrangement. RESULTS: Single-site mutants of light-chain variable domain Len, designated LenQ38E and LenK30T, formed 'flipped' dimers in which one domain was rotated by about 180 degrees compared with the native protein. The dimer in the native protein is similar to that found between variable domains in Fab immunoglobulin fragments. When compared to the native dimer, more surface area is buried, and more hydrogen bonds and salt bridges are formed between the monomers in the flipped conformation. CONCLUSIONS: Immunoglobulin light-chain variable domains can form a minimum of two distinct quaternary structures. Single-site mutations resulting from changes of one base, such as the exchange of Gln38 to Glu or Lys30 to Thr, change the 'conventional' dimer of protein Len to a flipped arrangement. Native Len is not found in the flipped-domain dimer conformation because it would have excess positive electrostatic potential at the dimer interface that is not compensated by other forces. Excess negative or positive electrostatic potential at the dimer interface can have a determining effect on the mode of dimerization.

Selected figure(s)

Figure 2.
Figure 2. Cross sections of the two dimers near residue 38. (a) Section of the Len dimer perpendicular to the twofold axis between the domains. Gln38 of each monomer forms hydrogen bonds with the other monomer's Gln38 across the twofold axis. (b) Section of the LenQ38E dimer perpendicular to the twofold axis between the domains, illustrating the complementarity of the domains. Internal water molecules connect each Tyr36 to carbonyls of residues 44. The closest distance between charged residues Lys30 and Glu38 is 11 å. (This figure was generated using the program SETOR [28].)

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1067-1073) copyright 1998.

Figure was selected by an automated process.