Structure of Vibrio Collagenase VhaC Provides Insight into the Mechanism of Bacterial Collagenolysis

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jan 29

PMID 35091565

Authors

Yan Wang

Peng Wang

Hai-Yan Cao

Hai-Tao Ding

Hai-Nan Su

Shi-Cheng Liu

Guangfeng Liu

Xia Zhang

Chun-Yang Li

Ming Peng

Fuchuan Li

Shengying Li

Yin Chen

Xiu-Lan Chen

Yu-Zhong Zhang

Affiliations

Soon will be listed here.

Abstract

The collagenases of Vibrio species, many of which are pathogens, have been regarded as an important virulence factor. However, there is little information on the structure and collagenolytic mechanism of Vibrio collagenase. Here, we report the crystal structure of the collagenase module (CM) of Vibrio collagenase VhaC and the conformation of VhaC in solution. Structural and biochemical analyses and molecular dynamics studies reveal that triple-helical collagen is initially recognized by the activator domain, followed by subsequent cleavage by the peptidase domain along with the closing movement of CM. This is different from the peptidolytic mode or the proposed collagenolysis of Clostridium collagenase. We propose a model for the integrated collagenolytic mechanism of VhaC, integrating the functions of VhaC accessory domains and its collagen degradation pattern. This study provides insight into the mechanism of bacterial collagenolysis and helps in structure-based drug design targeting of the Vibrio collagenase.

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References

Shoulders M, Raines R . Collagen structure and stability. Annu Rev Biochem. 2009; 78:929-58. PMC: 2846778. DOI: 10.1146/annurev.biochem.77.032207.120833. View

Orgel J, Irving T, Miller A, Wess T . Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci U S A. 2006; 103(24):9001-5. PMC: 1473175. DOI: 10.1073/pnas.0502718103. View

Perumal S, Antipova O, Orgel J . Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis. Proc Natl Acad Sci U S A. 2008; 105(8):2824-9. PMC: 2268544. DOI: 10.1073/pnas.0710588105. View

Gelse K, Poschl E, Aigner T . Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003; 55(12):1531-46. DOI: 10.1016/j.addr.2003.08.002. View

Scott J . Proteoglycan-fibrillar collagen interactions. Biochem J. 1988; 252(2):313-23. PMC: 1149146. DOI: 10.1042/bj2520313. View

Orgel J, Eid A, Antipova O, Bella J, Scott J . Decorin core protein (decoron) shape complements collagen fibril surface structure and mediates its binding. PLoS One. 2009; 4(9):e7028. PMC: 2737631. DOI: 10.1371/journal.pone.0007028. View

Duarte A, Correia A, Esteves A . Bacterial collagenases - A review. Crit Rev Microbiol. 2014; 42(1):106-26. DOI: 10.3109/1040841X.2014.904270. View

Nagase H, Visse R, Murphy G . Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3):562-73. DOI: 10.1016/j.cardiores.2005.12.002. View

Fields G . Interstitial collagen catabolism. J Biol Chem. 2013; 288(13):8785-93. PMC: 3610953. DOI: 10.1074/jbc.R113.451211. View

10.

Iyer S, Visse R, Nagase H, Acharya K . Crystal structure of an active form of human MMP-1. J Mol Biol. 2006; 362(1):78-88. PMC: 1885970. DOI: 10.1016/j.jmb.2006.06.079. View

11.

Lauer-Fields J, Chalmers M, Busby S, Minond D, Griffin P, Fields G . Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity. J Biol Chem. 2009; 284(36):24017-24. PMC: 2781996. DOI: 10.1074/jbc.M109.016873. View

12.

Bertini I, Fragai M, Luchinat C, Melikian M, Mylonas E, Sarti N . Interdomain flexibility in full-length matrix metalloproteinase-1 (MMP-1). J Biol Chem. 2009; 284(19):12821-8. PMC: 2676012. DOI: 10.1074/jbc.M809627200. View

13.

Arnold L, Butt L, Prior S, Read C, Fields G, Pickford A . The interface between catalytic and hemopexin domains in matrix metalloproteinase-1 conceals a collagen binding exosite. J Biol Chem. 2011; 286(52):45073-82. PMC: 3247971. DOI: 10.1074/jbc.M111.285213. View

14.

Cerofolini L, Fields G, Fragai M, Geraldes C, Luchinat C, Parigi G . Examination of matrix metalloproteinase-1 in solution: a preference for the pre-collagenolysis state. J Biol Chem. 2013; 288(42):30659-30671. PMC: 3798536. DOI: 10.1074/jbc.M113.477240. View

15.

Bertini I, Fragai M, Luchinat C, Melikian M, Toccafondi M, Lauer J . Structural basis for matrix metalloproteinase 1-catalyzed collagenolysis. J Am Chem Soc. 2012; 134(4):2100-10. PMC: 3298817. DOI: 10.1021/ja208338j. View

16.

Fasciglione G, Gioia M, Tsukada H, Liang J, Iundusi R, Tarantino U . The collagenolytic action of MMP-1 is regulated by the interaction between the catalytic domain and the hinge region. J Biol Inorg Chem. 2012; 17(4):663-72. DOI: 10.1007/s00775-012-0886-z. View

17.

Harrington D . Bacterial collagenases and collagen-degrading enzymes and their potential role in human disease. Infect Immun. 1996; 64(6):1885-91. PMC: 174012. DOI: 10.1128/iai.64.6.1885-1891.1996. View

18.

Zhang Y, Ran L, Li C, Chen X . Diversity, Structures, and Collagen-Degrading Mechanisms of Bacterial Collagenolytic Proteases. Appl Environ Microbiol. 2015; 81(18):6098-107. PMC: 4542243. DOI: 10.1128/AEM.00883-15. View

19.

Eckhard U, Schonauer E, Nuss D, Brandstetter H . Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis. Nat Struct Mol Biol. 2011; 18(10):1109-14. PMC: 3191118. DOI: 10.1038/nsmb.2127. View

20.

Eckhard U, Schonauer E, Brandstetter H . Structural basis for activity regulation and substrate preference of clostridial collagenases G, H, and T. J Biol Chem. 2013; 288(28):20184-94. PMC: 3711286. DOI: 10.1074/jbc.M112.448548. View