6FZV

Crystal structure of the metalloproteinase enhancer PCPE-1 bound to the procollagen C propeptide trimer (short)

Summary for 6FZV

• Entry DOI: 10.2210/pdb6fzv/pdb
• Descriptor: Collagen alpha-1(III) chain, Procollagen C-endopeptidase enhancer 1, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: collagen, structural protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 115981.52

Authors

Pulido, D.,Hohenester, E. (deposition date: 2018-03-15, release date: 2018-07-04, Last modification date: 2024-10-23)

Primary citation

Pulido, D.,Sharma, U.,Vadon-Le Goff, S.,Hussain, S.A.,Cordes, S.,Mariano, N.,Bettler, E.,Moali, C.,Aghajari, N.,Hohenester, E.,Hulmes, D.J.S.
Structural Basis for the Acceleration of Procollagen Processing by Procollagen C-Proteinase Enhancer-1.
Structure, 26:1384-1392.e3, 2018

PubMed Abstract: Procollagen C-proteinase enhancer-1 (PCPE-1) is a secreted protein that specifically accelerates proteolytic release of the C-propeptides from fibrillar procollagens, a crucial step in fibril assembly. As such, it is a potential therapeutic target to improve tissue repair and prevent fibrosis, a major cause of mortality worldwide. Here we present the crystal structure of the active CUB1CUB2 fragment of PCPE-1 bound to the C-propeptide trimer of procollagen III (CPIII). This shows that the two CUB domains bind to two different chains of CPIII and that the N-terminal region of one CPIII chain, close to the proteolytic cleavage site, lies in the cleft between CUB1 and CUB2. This suggests that enhancing activity involves unraveling of this chain from the rest of the trimer, thus facilitating the action of the proteinase involved. Support for this hypothesis comes from site-directed mutagenesis, enzyme assays, binding studies, and molecular modeling.

PubMed: 30078642
DOI: 10.1016/j.str.2018.06.011

Experimental method

X-RAY DIFFRACTION (2.7 Å)