Jordi Bella

Manchester Academic Health Science Centre

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Michael G. Rossmann

Purdue University West Lafayette

Helen Berman

Rutgers, The State University of New Jersey

Paul McEwan

Evotec (United Kingdom)

Prasanna R. Kolatkar

Hamad bin Khalifa University

Barbara Brodsky

Tufts University

Paul N. Bishop

University of Manchester

Lydia Tabernero

Manchester Academic Health Science Centre

Stephen M. Richardson

University of Manchester

Mattia Vitale

University of Manchester

R. Kramer

Rutgers, The State University of New Jersey

Cooperative Institutions

University of Manchester

Wellcome Centre for Cell-Matrix Research

Manchester Academic Health Science Centre

Purdue University West Lafayette

Henry Royce Institute

Universitat Politècnica de Catalunya

Rutgers, The State University of New Jersey

Consejo Superior de Investigaciones Científicas

Miles College

Manchester University NHS Foundation Trust

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Collagen structure: new tricks from a very old dog

Biochemical Journal (2016)

Jordi Bella

The main features of the triple helical structure of collagen were deduced in the mid-1950s from fibre X-ray diffraction of tendons. Yet, the resulting models only could offer an average description of the molecular conformation. A critical advance came about 20 years later with the chemical synthesis of sufficiently long and homogeneous peptides with collagen-like sequences. The availability of these collagen model peptides resulted in a large number of biochemical, crystallographic and NMR studies that have revolutionized our understanding of collagen structure. High-resolution crystal structures from collagen model peptides have provided a wealth of data on collagen conformational variability, interaction with water, collagen stability or the effects of interruptions. Furthermore, a large increase in the number of structures of collagen model peptides in complex with domains from receptors or collagen-binding proteins has shed light on the mechanisms of collagen recognition. In recent years, collagen biochemistry has escaped the boundaries of natural collagen sequences. Detailed knowledge of collagen structure has opened the field for protein engineers who have used chemical biology approaches to produce hyperstable collagens with unnatural residues, rationally designed collagen heterotrimers, self-assembling collagen peptides, etc. This review summarizes our current understanding of the structure of the collagen triple helical domain (COL×3) and gives an overview of some of the new developments in collagen molecular engineering aiming to produce novel collagen-based materials with superior properties.

Collagen helix

Collagen fibril

Structural Biology

Type I collagen

10.1042/bj20151169

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Citations (220)

CRYSTAL STRUCTURE ANALYSIS OF NORWALK VIRUS CAPSID

B. V. Venkataram Prasad M. E. Hardy Terje Dokland Jordi Bella M.G. Rossmann

Norwalk virus

10.2210/pdb1ihm/pdb

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Citations (0)

The leucine-rich repeat structure

Cellular and Molecular Life Sciences (2008)

Jordi Bella K. Lauren Hindle Paul McEwan Simon C. Lovell

Leucine-rich repeat

Structural motif

Protein design

Protein Engineering

10.1007/s00018-008-8019-0

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Citations (439)

Decorin Core Protein (Decoron) Shape Complements Collagen Fibril Surface Structure and Mediates Its Binding

PLoS ONE (2009)

Joseph Orgel Aya Eid Olga Antipova Jordi Bella J. E. Scott

Decorin is the archetypal small leucine rich repeat proteoglycan of the vertebrate extracellular matrix (ECM). With its glycosaminoglycuronan chain, it is responsible for stabilizing inter-fibrillar organization. Type I collagen is the predominant member of the fibrillar collagen family, fulfilling both organizational and structural roles in animal ECMs. In this study, interactions between decoron (the decorin core protein) and binding sites in the d and e1 bands of the type I collagen fibril were investigated through molecular modeling of their respective X-ray diffraction structures. Previously, it was proposed that a model-based, highly curved concave decoron interacts with a single collagen molecule, which would form extensive van der Waals contacts and give rise to strong non-specific binding. However, the large well-ordered aggregate that is the collagen fibril places significant restraints on modes of ligand binding and necessitates multi-collagen molecular contacts. We present here a relatively high-resolution model of the decoron-fibril collagen complex. We find that the respective crystal structures complement each other well, although it is the monomeric form of decoron that shows the most appropriate shape complementarity with the fibril surface and favorable calculated energies of interaction. One molecule of decoron interacts with four to six collagen molecules, and the binding specificity relies on a large number of hydrogen bonds and electrostatic interactions, primarily with the collagen motifs KXGDRGE and AKGDRGE (d and e1 bands). This work helps us to understand collagen-decorin interactions and the molecular architecture of the fibrillar ECM in health and disease.

10.1371/journal.pone.0007028

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Citations (144)

Polyamides with a structure related to polyglycine

Peptides (1991)

Jordi Bella Jordi Puiggalı́Juan A. Subirana

10.1007/978-94-011-3034-9_189

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Citations (1)

Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan

Proceedings of the National Academy of Sciences (2004)

Paul G. Scott Paul McEwan Carole M. Dodd Ernst M. Bergmann Paul N. Bishop

Decorin is a ubiquitous extracellular matrix proteoglycan with a variety of important biological functions that are mediated by its interactions with extracellular matrix proteins, cytokines, and cell surface receptors. Decorin is the prototype of the family of small leucine-rich repeat proteoglycans and proteins (SLRPs), characterized by a protein core composed of leucine-rich repeats (LRRs), flanked by two cysteine-rich regions. We report here the crystal structure of the dimeric protein core of decorin, the best characterized member of the SLRP family. Each monomer adopts the curved solenoid fold characteristic of LRR domains, with a parallel beta-sheet on the inside interwoven with loops containing short segments of beta-strands, 3(10) helices, and polyproline II helices on the outside. Two main features are unique to this structure. First, decorin dimerizes through the concave surfaces of the LRR domains, which have been implicated previously in protein-ligand interactions. The amount of surface buried in this dimer rivals the buried surfaces of some of the highest-affinity macromolecular complexes reported to date. Second, the C-terminal region adopts an unusual capping motif that involves a laterally extended LRR and a disulfide bond. This motif seems to be unique to SLRPs and has not been observed in any other LRR protein structure to date. Possible implications of these features for decorin ligand binding and SLRP function are discussed.

Leucine-rich repeat

10.1073/pnas.0402976101

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Citations (213)

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Frontiers in Cell and Developmental Biology (2021)

Iva R. Nedeva Mattia Vitale Ari Elson Judith A. Hoyland Jordi Bella

Formation of mature bone-resorbing cells through osteoclastogenesis is required for the continuous remodeling and repair of bone tissue. In aging and disease this process may become aberrant, resulting in excessive bone degradation and fragility fractures. Interaction of receptor-activator of nuclear factor-κB (RANK) with its ligand RANKL activates the main signaling pathway for osteoclastogenesis. However, compelling evidence indicates that this pathway may not be sufficient for the production of mature osteoclast cells and that co-stimulatory signals may be required for both the expression of osteoclast-specific genes and the activation of osteoclasts. Osteoclast-associated receptor (OSCAR), a regulator of osteoclast differentiation, provides one such co-stimulatory pathway. This review summarizes our present knowledge of osteoclastogenesis signaling and the role of OSCAR in the normal production of bone-resorbing cells and in bone disease. Understanding the signaling mechanism through this receptor and how it contributes to the production of mature osteoclasts may offer a more specific and targeted approach for pharmacological intervention against pathological bone resorption.

RANK Ligand

Bone remodeling

10.3389/fcell.2021.641162

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Citations (44)

Crystallographic Evidence for Cα–H···O=C Hydrogen Bonds in a Collagen Triple Helix

Journal of Molecular Biology (1996)

Jordi Bella Helen Berman

Collagen helix

Helix (gastropod)

Triple bond

Globular protein