Characterization of the Nucleation Step and Folding of a Collagen Triple-Helix Peptide†

Biochemistry ◽  
2002 ◽  
Vol 41 (25) ◽  
pp. 8143-8151 ◽  
Author(s):  
Yujia Xu ◽  
Manjiri Bhate ◽  
Barbara Brodsky
Keyword(s):  
Triple Helix ◽  
Collagen Triple Helix

scholarly journals Characterization of three osteogenesis imperfecta collagen α 1(I) glycine to serine mutations demonstrating a position-dependent gradient of phenotypic severity

1992 ◽  
Vol 288 (1) ◽  
pp. 131-135 ◽  
Author(s):  
J F Bateman ◽  
I Moeller ◽  
M Hannagan ◽  
D Chan ◽  
W G Cole
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Type I ◽  
Disruptive Effect ◽  
Collagen Triple Helix ◽  
C Terminus ◽  
Glycine Substitution ◽  
C And N

Type I collagen alpha 1(I) glycine to serine substitutions, resulting from G-to-A mutations, were defined in three cases of osteogenesis imperfecta (OI). The Gly substitutions displayed a gradient of phenotypic severity according to the location of the mutation in the collagen triple helix. The most C-terminal of these, Gly565 to Ser, led to the lethal perinatal (type II) form of OI, whereas the more N-terminal mutations, Gly415 and Gly352 to Ser, led to severe OI (type III/IV) and moderate OI (type IVB) respectively. These data support the notion that glycine substitutions towards the C-terminus of the alpha 1(I) or alpha 2(I) chains will be more clinically severe than those towards the N-terminus. This results from the more disruptive effect of the mutations at the C-terminus on helix initiation and C- and N-terminal helix directional propagation. This generalization must be modified by considering the nature of the glycine substitution and the surrounding amino acid sequence, since the helix is composed of subdomains of differing stability which will affect the ability of helix re-nucleation and propagation.

Photocontrol of the Collagen Triple Helix: Synthesis and Conformational Characterization of Bis-cysteinyl Collagenous Peptides with an Azobenzene Clamp

2007 ◽  
Vol 13 (10) ◽  
pp. 2966-2973 ◽  
Author(s):  
Ulrike Kusebauch ◽  
Sergio A. Cadamuro ◽  
Hans-Jürgen Musiol ◽  
Luis Moroder ◽  
Christian Renner
Keyword(s):  
Triple Helix ◽  
Collagen Triple Helix

scholarly journals Mini-collagens in hydra nematocytes.

1991 ◽  
Vol 115 (4) ◽  
pp. 1159-1169 ◽  
Author(s):  
E M Kurz ◽  
T W Holstein ◽  
B M Petri ◽  
J Engel ◽  
C N David
Keyword(s):  
Amino Acid ◽  
Central Region ◽  
Triple Helix ◽  
Amino Acid Sequences ◽  
Disulfide Linkage ◽  
Amino Terminal ◽  
Collagen Triple Helix ◽  
Polyproline Ii ◽  
Carboxy Terminal

We have isolated and characterized four collagen-related c-DNA clones (N-COL 1, N-COL 2, N-COL 3, N-COL 4) that are highly expressed in developing nematocytes in hydra. All four c-DNAs as well as their corresponding transcripts are small in size (600-1,000 bp). The deduced amino acid sequences show that they contain a central region consisting of 14 to 16 Gly-X-Y triplets. This region is flanked amino-terminal by a stretch of 14-23 proline residues and carboxy-terminal by a stretch of 6-9 prolines. At the NH2- and COOH-termini are repeated patterns of cysteine residues that are highly conserved between the molecules. A model is proposed which consists of a central stable collagen triple helix of 12-14 nm length from which three 9-22 nm long polyproline II type helices emerge at both ends. Disulfide linkage between cysteine-rich segments in these helices could lead to the formation of oligomeric network structures. Electrophoretic characterization of nematocyst extracts allows resolution of small proline-rich polypeptides that correspond in size to the cloned sequences.

scholarly journals The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Targets ◽  
Triple Helix ◽  
Cancer Metastasis ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Patient Treatment ◽  
Collagen Triple Helix ◽  
Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

Comparative NMR Analysis of Collagen Triple Helix Organization from N- to C-Termini

2014 ◽  
Vol 16 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Amanda M. Acevedo-Jake ◽  
Abhishek A. Jalan ◽  
Jeffrey D. Hartgerink
Keyword(s):  
Triple Helix ◽  
Nmr Analysis ◽  
Collagen Triple Helix

scholarly journals Burkholderia collagen-like protein 8, Bucl8, is a unique outer membrane component of a tetrapartite efflux pump in Burkholderia pseudomallei and Burkholderia mallei

2020 ◽  
Author(s):  
Megan E Grund ◽  
Soo J Choi ◽  
Dudley H McNitt ◽  
Mariette Barbier ◽  
Gangqing Hu ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Burkholderia Pseudomallei ◽  
Triple Helix ◽  
Efflux Pump ◽  
Fusaric Acid ◽  
Efflux Pumps ◽  
Resistant Bacteria ◽  
Burkholderia Mallei ◽  
Membrane Component ◽  
Collagen Triple Helix

AbstractBacterial efflux pumps are an important pathogenicity trait because they extrude a variety of xenobiotics. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) in the Tier one select agents Burkholderia pseudomallei and Burkholderia mallei. We hypothesize that Bucl8, which contains two predicted tandem outer membrane efflux pump domains, is a component of a putative efflux pump. Unique to Bucl8, as compared to other outer membrane proteins, is the presence of an extended extracellular region containing a collagen-like (CL) domain and a non-collagenous C-terminus (Ct). Molecular modeling and circular dichroism spectroscopy with a recombinant protein, corresponding to this extracellular CL-Ct portion of Bucl8, demonstrated that it adopts a collagen triple helix, whereas functional assays screening for Bucl8 ligands identified binding to fibrinogen. Bioinformatic analysis of the bucl8 gene locus revealed it resembles a classical efflux-pump operon. The bucl8 gene is co-localized with downstream fusCDE genes encoding fusaric acid (FA) resistance, and with an upstream gene, designated as fusR, encoding a LysR-type transcriptional regulator. Using RT-qPCR, we defined the boundaries and transcriptional organization of the fusR-bucl8-fusCDE operon. We found exogenous FA induced bucl8 transcription over 80-fold in B. pseudomallei, while deletion of the entire bucl8 locus decreased the MIC of FA 4-fold in its isogenic mutant. We furthermore showed that the Bucl8 pump expressed in the heterologous Escherichia coli host confers FA resistance. On the contrary, the Bucl8 pump did not confer resistance to a panel of clinically-relevant antimicrobials in Burkholderia and E. coli. We finally demonstrated that deletion of the bucl8-locus drastically affects the growth of the mutant in L-broth. We determined that Bucl8 is a component of a novel tetrapartite efflux pump, which confers FA resistance, fibrinogen binding, and optimal growth.Author SummaryBurkholderia pseudomallei and Burkholderia mallei are highly infectious and multidrug resistant bacteria that are classified by the National Institute of Allergy and Infectious Diseases as Tier one select agents partly due to the intrinsic multidrug resistance associated with expression of the efflux pumps. To date, only few efflux pumps predicted in Burkholderia spp. have been studied in detail. In the current study we introduce Bucl8, an outer membrane component of an unreported putative efflux pump with a unique extended extracellular portion that forms a collagen triple helix and binds fibrinogen. We demonstrate Bucl8’s role in fusaric acid resistance by defining its operon via bioinformatic and transcriptional analyses, as well as by employing loss-of-function and gain-of-function genetic approaches. Our studies also implicate the Bucl8-associated pump in metabolic and physiologic homeostasis. Understanding how Bucl8 efflux pump contributes to Burkholderia pathology will foster development of pump inhibitors targeting transport mechanism or identifying potential surface-exposed vaccine targets.

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