ll species of vertebrates synthesize immunoglobulin molecules, which differ in an number of aspects but also share a few common features responsible for their function, such as the presence of a transmembrane domain in the membrane bound form of the immunoglobulin heavy chain (IgTMD) that ensures communication with the signal transducing Igα-Igβ peptides. We have analyzed the gene sequence encoding the IgTMD of different heavy chain isotypes of very distant species, from shark to mammals. The IgTMD sequences show a high degree of sequence identity and their encoding nucleotide sequences were shown to be subject to purifying selection at most sites. We have built molecular models of seven IgTMDs from different vertebrate species and have investigated the formation of homodimer in a palmitoyl oleoyl phosphatidylcholine (POPC) lipid bilayer by molecular dynamics simulations. We found that the conserved FXXXFXXS/TXXXS motif, never observed to date in protein transmembrane chains, is responsible for the two heavy chains association through two pairs of Phe-Phe hydrophobic interactions and two pairs of Ser/Thr-Ser/Ser hydrogen bonds. This interaction pattern, which stabilizes the dimer conformation in the lipid bilayer, was unique, being different from any other pattern identified in transmembrane helices to date

An evolutionary conserved motif is responsible for the Immunoglobulin heavy chains packing in the B cell membrane

MERLINO, ANTONELLO;MAZZARELLA, LELIO;
2010

Abstract

ll species of vertebrates synthesize immunoglobulin molecules, which differ in an number of aspects but also share a few common features responsible for their function, such as the presence of a transmembrane domain in the membrane bound form of the immunoglobulin heavy chain (IgTMD) that ensures communication with the signal transducing Igα-Igβ peptides. We have analyzed the gene sequence encoding the IgTMD of different heavy chain isotypes of very distant species, from shark to mammals. The IgTMD sequences show a high degree of sequence identity and their encoding nucleotide sequences were shown to be subject to purifying selection at most sites. We have built molecular models of seven IgTMDs from different vertebrate species and have investigated the formation of homodimer in a palmitoyl oleoyl phosphatidylcholine (POPC) lipid bilayer by molecular dynamics simulations. We found that the conserved FXXXFXXS/TXXXS motif, never observed to date in protein transmembrane chains, is responsible for the two heavy chains association through two pairs of Phe-Phe hydrophobic interactions and two pairs of Ser/Thr-Ser/Ser hydrogen bonds. This interaction pattern, which stabilizes the dimer conformation in the lipid bilayer, was unique, being different from any other pattern identified in transmembrane helices to date
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/374793
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact