PDBsum entry 5nir

Structural protein

PDB id: 5nir

Contents

Protein chains

69 a.a.

Ligands

EDO ×8

PEG ×7

PG4 ×6

P33

Waters ×16

PDB id:

5nir

Name:

Structural protein

Title:

Crystal structure of collagen 2a vwc domain

Structure:

Collagen alpha-1(ii) chain. Chain: a, b. Synonym: alpha-1 type ii collagen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: col2a1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.74Å R-factor: 0.210 R-free: 0.231

Authors:

G.Fischer,E.Blythe,M.Hyvonen

Key ref:

E.R.Xu et al. (2017). Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2. J Biol Chem, 292, 12516-12527. PubMed id: 28584056

Date:

27-Mar-17 Release date: 14-Jun-17

Protein chains

P02458  (CO2A1_HUMAN) -  Collagen alpha-1(II) chain from Homo sapiens

Seq: 1487 a.a.

Struc: 69 a.a.

J Biol Chem 292:12516-12527 (2017)

PubMed id: 28584056

Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2.

E.R.Xu, E.E.Blythe, G.Fischer, M.Hyvönen.

ABSTRACT

Bone morphogenetic proteins (BMPs) are secreted growth factors that promote differentiation processes in embryogenesis and tissue development. Regulation of BMP signaling involves binding to a variety of extracellular proteins, among which are many von Willebrand factor C (vWC) domain-containing proteins. Although the crystal structure of the complex of crossveinless-2 (CV-2) vWC1 and BMP-2 previously revealed one mode of the vWC/BMP-binding mechanism, other vWC domains may bind to BMP differently. Here, using X-ray crystallography, we present for the first time structures of the vWC domains of two proteins thought to interact with BMP-2: collagen IIA and matricellular protein CCN3. We found that these two vWC domains share a similar N-terminal fold that differs greatly from that in CV-2 vWC, which comprises its BMP-2-binding site. We analyzed the ability of these vWC domains to directly bind to BMP-2 and detected an interaction only between the collagen IIa vWC and BMP-2. Guided by the collagen IIa vWC domain crystal structure and conservation of surface residues among orthologous domains, we mapped the BMP-binding epitope on the subdomain 1 of the vWC domain. This binding site is different from that previously observed in the complex between CV-2 vWC and BMP-2, revealing an alternative mode of interaction between vWC domains and BMPs.