MDPI - Publisher of Open Access Journals

13 pages, 3360 KiB

Open AccessArticle

Disrupting Effects of Osteogenesis Imperfecta Mutations Could Be Predicted by Local Hydrogen Bonding Energy

by Shumin Qiang, Cheng Lu and Fei Xu

Biomolecules 2022, 12(8), 1104; https://doi.org/10.3390/biom12081104 - 11 Aug 2022

Cited by 7 | Viewed by 3266

Osteogenesis imperfecta(OI) is a disease caused by substitution in glycine residues with different amino acids in type I collagen (Gly-Xaa-Yaa)n. Collagen model peptides can capture the thermal stability loss of the helix after Gly mutations, most of which are homotrimers. However, a majority of natural collagen exists in heterotrimers. To investigate the effects of chain specific mutations in the natural state of collagen more accurately, here we introduce various lengths of side-chain amino acids into ABC-type heterotrimers. The disruptive effects of the mutations were characterized both experimentally and computationally. We found the stability decrease in the mutants was mainly caused by the disruption of backbone hydrogen bonds. Meanwhile, we found a threshold value of local hydrogen bonding energy that could predict triple helix folding or unfolding. Val caused the unfolding of triple helices, whereas Ser with a similar side-chain length did not. Structural details suggested that the side-chain hydroxyl group in Ser forms hydrogen bonds with the backbone, thereby compensating for the mutants’ decreased stability. Our study contributes to a better understanding of how OI mutations destabilize collagen triple helices and the molecular mechanisms underlying OI. Full article

(This article belongs to the Topic Computer-Based Solutions to Investigate Biological- and Health-Related Problems)

► Show Figures

Figure 1

24 pages, 3948 KiB

Open AccessEditor’s ChoiceReview

Collagen Mimetic Peptides

by Yujia Xu and Michele Kirchner

Bioengineering 2021, 8(1), 5; https://doi.org/10.3390/bioengineering8010005 - 5 Jan 2021

Cited by 52 | Viewed by 13038

Abstract

Since their first synthesis in the late 1960s, collagen mimetic peptides (CMPs) have been used as a molecular tool to study collagen, and as an approach to develop novel collagen mimetic biomaterials. Collagen, a major extracellular matrix (ECM) protein, plays vital roles in many physiological and pathogenic processes. Applications of CMPs have advanced our understanding of the structure and molecular properties of a collagen triple helix—the building block of collagen—and the interactions of collagen with important molecular ligands. The accumulating knowledge is also paving the way for developing novel CMPs for biomedical applications. Indeed, for the past 50 years, CMP research has been a fast-growing, far-reaching interdisciplinary field. The major development and achievement of CMPs were documented in a few detailed reviews around 2010. Here, we provided a brief overview of what we have learned about CMPs—their potential and their limitations. We focused on more recent developments in producing heterotrimeric CMPs, and CMPs that can form collagen-like higher order molecular assemblies. We also expanded the traditional view of CMPs to include larger designed peptides produced using recombinant systems. Studies using recombinant peptides have provided new insights on collagens and promoted progress in the development of collagen mimetic fibrillar self-assemblies. Full article

(This article belongs to the Special Issue Biomedical Applications of Collagen)

► Show Figures

Figure 1

Search Results (2)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (2)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI