title: Diversified Structural Basis of a Conserved Molecular Mechanism for pH-Dependent Dimerization in Spider Silk N-Terminal Domains.
abstract: Conversion of spider silk proteins from soluble dope to insoluble fibers involves pH-dependent dimerization of the N-terminal domain (NT). This conversion is tightly regulated to prevent premature precipitation and enable rapid silk formation at the end of the duct. Three glutamic acid residues that mediate this process in the NT from Euprosthenops australis major ampullate spidroin 1 are well conserved among spidroins. However, NTs of minor ampullate spidroins from several species, including Araneus ventricosus ((Av)MiSp NT), lack one of the glutamic acids. Here we investigate the pH-dependent structural changes of (Av)MiSp NT, revealing that it uses the same mechanism but involves a non-conserved glutamic acid residue instead. Homology modeling of the structures of other MiSp NTs suggests that these harbor different compensatory residues. This indicates that, despite sequence variations, the molecular mechanism underlying pH-dependent dimerization of NT is conserved among different silk types.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga (Latvia).
authors.forename: Martins
authors.initials: M
authors.lastname: Otikovs
authors.affiliation: Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Novum, 141 57 Huddinge (Sweden).|Institute of Biological Sciences and Biotechnology, Donghua University, 201620 Shanghai (China).
authors.forename: Gefei
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Novum, 141 57 Huddinge (Sweden).
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nordling
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm (Sweden).|Present address: Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 5QY (UK).
authors.forename: Michael
authors.initials: M
authors.lastname: Landreh
authors.affiliation: Institute of Biological Sciences and Biotechnology, Donghua University, 201620 Shanghai (China).
authors.forename: Qing
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm (Sweden).
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.affiliation: Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Novum, 141 57 Huddinge (Sweden).
authors.forename: Nina
authors.initials: N
authors.lastname: Kronqvist
authors.affiliation: Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Novum, 141 57 Huddinge (Sweden).|Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, Box 575, 751 23 Uppsala (Sweden).
authors.forename: Anna
authors.initials: A
authors.lastname: Rising
authors.affiliation: Department of Neurobiology, Care Sciences and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Novum, 141 57 Huddinge (Sweden). janne.johansson@ki.se.|Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, Box 575, 751 23 Uppsala (Sweden). janne.johansson@ki.se.|Institute of Mathematics and Natural Sciences, Tallinn University, Narva mnt 25, 101 20 Tallinn (Estonia). janne.johansson@ki.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga (Latvia). kristaps.jaudzems@osi.lv.
authors.forename: Kristaps
authors.initials: K
authors.lastname: Jaudzems
mesh_terms: D000818:Animals; D019281:Dimerization; D005349:Fibroins / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017434:Protein Structure, Tertiary; D047011:Silk / Q000737:chemistry* / Q000378:metabolism; D013112:Spiders / Q000737:chemistry / Q000502:physiology*
chemical_list: D047011:Silk; D005349:Fibroins
keywords: NMR structure; pH sensitivity; protein conformation; spidroins