Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH
- Univ. of Arkansas, Fayetteville, AR (United States). Dept. of Chemistry and Biochemistry
- Okayama Univ. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (Japan)
Clostridium histolyticumcollagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca2+-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca2+-bound holo s2b (1.4 Å resolution,R= 15.0%,Rfree= 19.1%) and holo s2a (1.9 Å resolution,R= 16.3%,Rfree= 20.7%), as well as of Ca2+-free apo s2a (1.8 Å resolution,R= 20.7%,Rfree= 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution,R= 16.9%,Rfree= 21.2%; 1.6 Å resolution,R= 16.2%,Rfree= 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca2+pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3.B-factor analyses suggest that in the presence of Ca2+the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca2+binding. Conserved residues not only interact with Ca2+, but also position the Ca2+-interacting water molecule. Ca2+aligns the N-terminal linker approximately parallel to the major axis of the domain. Ca2+binding also increases stability against heat and guanidine hydrochloride, and may improve the longevity in the extracellular matrix. The results of this study will further assist in developing collagen-targeting vehicles for various signal molecules.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institutes of Health (NIH); National Science Foundation (NSF); USDOE
- OSTI ID:
- 1194219
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography (Online), Vol. 71, Issue 3; ISSN 1399-0047
- Publisher:
- International Union of CrystallographyCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Web of Science
Basic Fibroblast Growth Factor Fused with Tandem Collagen-Binding Domains from Clostridium histolyticum Collagenase ColG Increases Bone Formation
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journal | January 2018 |
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