Type I collagen fibrils form the principal structural elements of most connective tissues and determine their physical properties. A long term objective of this project has been to understand the basic events involved in the fibril assembly and organization processes. A second goal has been to delineate the details of the assembly of procollagen molecules from their individual pro alpha-chains and to determine the factors which regulate chain selection and registration. To achieve these objectives three specific studies are proposed. 1. The cotranslational processing and assembly of procollagen molecules. Nascent pro alpha-chains reside on complex polyribosomal aggregates and elongate with synthesis pauses. The nascent chains will be analyzed to determine pause loci and their relation to specific sequence, cotranslational modification, and chain association requirements. The role of the polysome aggregate in chain selection and registration will be studied as related to cytosolic, membrane protein, and intrinsic mRNA factors. Chick tendon fibroblasts, and 2 cell lines which produce only pro alpha 1- and pro alpha 2-chains, respectively, will be studied by biochemical an electron microscopic techniques. 2. The assembly of monomeric collagen into fibrils. D-periodic assembly is dominated by telopeptide-helix receptor interactions which may involve subtle conformational alterations in both domains. These will be examined by FTIR spectroscopy and other physical techniques during the fibril formation process. Intact and specific atelopeptide collagens, and synthetic telopeptide and helix region sequence models for the interaction systems will be studied. 3. The development of fibril organization. Collagen-interacting macromolecules of the extracellular matrix affect fibril architecture and organization. A theoretical framework for considering these interactions has been constructed and will guide EM studies examination of the effects of specific matrix polyanionic components on fibril organization. These studies all have the ultimate objective of providing insight into the nature of connective tissue dysfunctions.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Northwestern University at Chicago
Schools of Dentistry
United States
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Garrison-Kimmel, Shea; Hopkins, Philip F; Wetzel, Andrew et al. (2018) The origin of the diverse morphologies and kinematics of Milky Way-mass galaxies in the FIRE-2 simulations. Mon Not R Astron Soc 481:4133-4157
George, Anne; Veis, Arthur (2008) Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition. Chem Rev 108:4670-93
Malone, James P; Alvares, Keith; Veis, Arthur (2005) Structure and assembly of the heterotrimeric and homotrimeric C-propeptides of type I collagen: significance of the alpha2(I) chain. Biochemistry 44:15269-79
Malone, James P; Veis, Arthur (2004) Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix receptor. Biochemistry 43:15358-66
Malone, James P; George, Anne; Veis, Arthur (2004) Type I collagen N-telopeptides adopt an ordered structure when docked to their helix receptor during fibrillogenesis. Proteins 54:206-15
Qin, Chunlin; Brunn, Jan C; Cook, Richard G et al. (2003) Evidence for the proteolytic processing of dentin matrix protein 1. Identification and characterization of processed fragments and cleavage sites. J Biol Chem 278:34700-8
Dahl, Thomas; Veis, Arthur (2003) Electrostatic interactions lead to the formation of asymmetric collagen-phosphophoryn aggregates. Connect Tissue Res 44 Suppl 1:206-13
Alvares, K; Siddiqui, F; Malone, J et al. (1999) Assembly of the type 1 procollagen molecule: selectivity of the interactions between the alpha 1(I)- and alpha 2(I)-carboxyl propeptides. Biochemistry 38:5401-11
Dahl, T; Sabsay, B; Veis, A (1998) Type I collagen-phosphophoryn interactions: specificity of the monomer-monomer binding. J Struct Biol 123:162-8
Gura, T; Hu, G; Veis, A (1996) Posttranscriptional aspects of the biosynthesis of type 1 collagen pro-alpha chains: the effects of posttranslational modifications on synthesis pauses during elongation of the pro alpha 1 (I) chain. J Cell Biochem 61:194-215

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