title: A new triple-stranded alpha-helical bundle in solution: the assembling of the cytosolic tail of MHC-associated invariant chain.
abstract: BACKGROUND
  The invariant chain (li) is a transmembrane protein that associates with the major histocompatibility complex class II (MHC II) molecules in the endoplasmic reticulum. The cytosolic tail of li contains two leucine-based sorting motifs and is involved in sorting the MHC II molecules to the endosomal pathway where the peptide antigen is bound. This region of li also contributes to phenotypical changes in cells, such as the formation of large endocytic structures.
  
  
  RESULTS
  We report here the three-dimensional structure of a 27 amino acid peptide corresponding to the cytosolic tail of li. The structure was determined by nuclear magnetic resonance (NMR) spectroscopy using a computational strategy. At high concentration, this structure reveals a new triple-stranded alpha-helical bundle in which the helices, two parallel and one antiparallel, are almost coplanar. Trimerization is mediated by electrostatic interactions intercalated by three hydrophobic layers.
  
  
  CONCLUSIONS
  The new trimer fold, the first to be identified by NMR data alone, can be used to improve understanding of protein-protein interactions and to model multiple-helical transmembrane proteins and receptors. We suggest that interactions of the li cytosolic tails may form part of a mechanism that could cause the endosomal retention and enlarged endosomes induced by li.
authors.affiliation: Istituto di Chimica di Molecole di Interesse Biologico del CNR (Istituto Nazionale di Chimica dei Sistemi Biologici), I-80072, Arco Felice, Italy. amot@nmr.icmib.na.cnr.it
authors.forename: A
authors.initials: A
authors.lastname: Motta
authors.forename: P
authors.initials: P
authors.lastname: Amodeo
authors.forename: P
authors.initials: P
authors.lastname: Fucile
authors.forename: M A
authors.initials: MA
authors.lastname: Castiglione Morelli
authors.forename: B
authors.initials: B
authors.lastname: Bremnes
authors.forename: O
authors.initials: O
authors.lastname: Bakke
mesh_terms: D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012996:Solutions
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D012996:Solutions; C045084:invariant chain