A DOMAIN FLIP AS A RESULT OF A SINGLE AMINO-ACID SUBSTITUTION

Citation
Pr. Pokkuluri et al., A DOMAIN FLIP AS A RESULT OF A SINGLE AMINO-ACID SUBSTITUTION, Structure, 6(8), 1998, pp. 1067-1073
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biophysics,Biology,"Cell Biology
Journal title
ISSN journal
0969-2126
Volume
6
Issue
8
Year of publication
1998
Pages
1067 - 1073
Database
ISI
SICI code
0969-2126(1998)6:8<1067:ADFAAR>2.0.ZU;2-#
Abstract
Background: The self-assembly properties of beta domains are important features of diverse classes of proteins that include cell-adhesion mo lecules, surface receptors and the immunoglobulin superfamily. Immunog lobulin light-chain variable domains are well suited to the study of s tructural factors that determine dimerization, including how residues at the interface influence the preferred dimer arrangement. Results: S ingle-site mutants of light-chain variable domain Len, designated LenQ 38E and LenK30T, formed 'flipped' dimers in which one domain was rotat ed 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, mo re surface area is buried, and more hydrogen bonds and salt bridges ar e formed between the monomers in the flipped conformation. Conclusions : Immunoglobulin light-chain variable domains can form a minimum of tw o 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 arra ngement. Native Len is not found in the flipped-domain dimer conformat ion because it would have excess positive electrostatic potential at t he dimer interface that is not compensated by other forces. Excess neg ative or positive electrostatic potential at the dimer interface can h ave a determining effect on the mode of dimerization.