title: Biological insertion of computationally designed short transmembrane segments.
abstract: The great majority of helical membrane proteins are inserted co-translationally into the ER membrane through a continuous ribosome-translocon channel. The efficiency of membrane insertion depends on transmembrane (TM) helix amino acid composition, the helix length and the position of the amino acids within the helix. In this work, we conducted a computational analysis of the composition and location of amino acids in transmembrane helices found in membrane proteins of known structure to obtain an extensive set of designed polypeptide segments with naturally occurring amino acid distributions. Then, using an in vitro translation system in the presence of biological membranes, we experimentally validated our predictions by analyzing its membrane integration capacity. Coupled with known strategies to control membrane protein topology, these findings may pave the way to de novo membrane protein design.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, ERI BioTecMed, Universitat de València. E-46100 Burjassot, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Baeza-Delgado
authors.affiliation: Dept. of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: von Heijne
authors.affiliation: CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Marti-Renom
authors.affiliation: Departament de Bioquímica i Biologia Molecular, ERI BioTecMed, Universitat de València. E-46100 Burjassot, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Mingarro
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D010455:Peptides / Q000235:genetics*; D017433:Protein Structure, Secondary
chemical_list: D008565:Membrane Proteins; D010455:Peptides