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Difference between revisions of "Carbohydrate Binding Module Family 14"

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With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14<sub>CHIT1</sub>). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14<sub>CHIT1</sub> also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14<sub>CHIT1</sub> and chitotriose is likely to occur through CH-&pi; stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.
 
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14<sub>CHIT1</sub>). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14<sub>CHIT1</sub> also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14<sub>CHIT1</sub> and chitotriose is likely to occur through CH-&pi; stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.
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CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)<sub>6</sub> <cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14<sub>CHIT1</sub> and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)<sub>6</sub> is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14. Mutational studies showed that binding to (GlcNAc)<sub>6</sub> was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-&pi; stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>.
 
== Functionalities ==  
 
== Functionalities ==  
 
''Content in this section should include, in paragraph form, a description of:''
 
''Content in this section should include, in paragraph form, a description of:''

Revision as of 06:09, 27 November 2020

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CAZy DB link
http://www.cazy.org/CBMnn.html

Ligand specificities

Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases [1] and as chitin-binding lectins e.g. an effector protein from the tomato pathogen Pseudoercospora fuligena or Cladosporium fulvum [2, 3], as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab haemocytes [4] and in peritrophic matrix proteins from Malaria vector Anopheles gambia [5]. Members of CBM14 have been shown to bind chitin [5, 6, 7] and chitooligomers [3, 8]. Binding to 50 % acetylated hyaluronan has also been demonstrated [8].

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 (GH18)) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM [8] and Kd 3.1 ± 0.2 mM [7], respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen C. fulvum and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM [3].

Structural Features

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn [2, 3]. The latter is also present in tachycitin [9]. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold [1, 3, 9].

With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM [10]. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module [8]. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported [7] to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end [7].

CBM14 from the tomato pathogen C. fulvum (CfCBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 [3]. Although the fold of CfCBM14 is the same as CBM14CHIT1 and other structurally characterized CBM14 members, the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of CfCBM14. Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively [3].

Functionalities

Content in this section should include, in paragraph form, a description of:

  • Functional role of CBM: Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
  • Most Common Associated Modules: 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
  • Novel Applications: Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

Family Firsts

First Identified
Insert archetype here, possibly including very brief synopsis.
First Structural Characterization
Insert archetype here, possibly including very brief synopsis.

References

  1. Fadel F, Zhao Y, Cousido-Siah A, Ruiz FX, Mitschler A, and Podjarny A. (2016). X-Ray Crystal Structure of the Full Length Human Chitotriosidase (CHIT1) Reveals Features of Its Chitin Binding Domain. PLoS One. 2016;11(4):e0154190. DOI:10.1371/journal.pone.0154190 | PubMed ID:27111557 [Fadel2016]
  2. Kohler AC, Chen LH, Hurlburt N, Salvucci A, Schwessinger B, Fisher AJ, and Stergiopoulos I. (2016). Structural Analysis of an Avr4 Effector Ortholog Offers Insight into Chitin Binding and Recognition by the Cf-4 Receptor. Plant Cell. 2016;28(8):1945-65. DOI:10.1105/tpc.15.00893 | PubMed ID:27401545 [Kohler2016]
  3. Hurlburt NK, Chen LH, Stergiopoulos I, and Fisher AJ. (2018). Structure of the Cladosporium fulvum Avr4 effector in complex with (GlcNAc)6 reveals the ligand-binding mechanism and uncouples its intrinsic function from recognition by the Cf-4 resistance protein. PLoS Pathog. 2018;14(8):e1007263. DOI:10.1371/journal.ppat.1007263 | PubMed ID:30148881 [Hurlburt2018]
  4. Kawabata S, Nagayama R, Hirata M, Shigenaga T, Agarwala KL, Saito T, Cho J, Nakajima H, Takagi T, and Iwanaga S. (1996). Tachycitin, a small granular component in horseshoe crab hemocytes, is an antimicrobial protein with chitin-binding activity. J Biochem. 1996;120(6):1253-60. DOI:10.1093/oxfordjournals.jbchem.a021549 | PubMed ID:9010778 [Kawabata1996]
  5. Shen Z and Jacobs-Lorena M. (1998). A type I peritrophic matrix protein from the malaria vector Anopheles gambiae binds to chitin. Cloning, expression, and characterization. J Biol Chem. 1998;273(28):17665-70. DOI:10.1074/jbc.273.28.17665 | PubMed ID:9651363 [Shen1998]
  6. Vandevenne M, Campisi V, Freichels A, Gillard C, Gaspard G, Frère JM, Galleni M, and Filée P. (2011). Comparative functional analysis of the human macrophage chitotriosidase. Protein Sci. 2011;20(8):1451-63. DOI:10.1002/pro.676 | PubMed ID:21674664 [Vandevenne2011]
  7. Madland E, Crasson O, Vandevenne M, Sørlie M, and Aachmann FL. (2019). NMR and Fluorescence Spectroscopies Reveal the Preorganized Binding Site in Family 14 Carbohydrate-Binding Module from Human Chitotriosidase. ACS Omega. 2019;4(26):21975-21984. DOI:10.1021/acsomega.9b03043 | PubMed ID:31891077 [Madland2019]
  8. Crasson O, Courtade G, Léonard RR, Aachmann FL, Legrand F, Parente R, Baurain D, Galleni M, Sørlie M, and Vandevenne M. (2017). Human Chitotriosidase: Catalytic Domain or Carbohydrate Binding Module, Who's Leading HCHT's Biological Function. Sci Rep. 2017;7(1):2768. DOI:10.1038/s41598-017-02382-z | PubMed ID:28584264 [Crasson2016]
  9. Suetake T, Tsuda S, Kawabata S, Miura K, Iwanaga S, Hikichi K, Nitta K, and Kawano K. (2000). Chitin-binding proteins in invertebrates and plants comprise a common chitin-binding structural motif. J Biol Chem. 2000;275(24):17929-32. DOI:10.1074/jbc.C000184200 | PubMed ID:10770921 [Suetake2000]
  10. Boraston AB, Bolam DN, Gilbert HJ, and Davies GJ. (2004). Carbohydrate-binding modules: fine-tuning polysaccharide recognition. Biochem J. 2004;382(Pt 3):769-81. DOI:10.1042/BJ20040892 | PubMed ID:15214846 [Boraston2004]
  11. van den Burg HA, Spronk CA, Boeren S, Kennedy MA, Vissers JP, Vuister GW, de Wit PJ, and Vervoort J. (2004). Binding of the AVR4 elicitor of Cladosporium fulvum to chitotriose units is facilitated by positive allosteric protein-protein interactions: the chitin-binding site of AVR4 represents a novel binding site on the folding scaffold shared between the invertebrate and the plant chitin-binding domain. J Biol Chem. 2004;279(16):16786-96. DOI:10.1074/jbc.M312594200 | PubMed ID:14769793 [Burg2004]
  12. Hollak CE, van Weely S, van Oers MH, and Aerts JM. (1994). Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest. 1994;93(3):1288-92. DOI:10.1172/JCI117084 | PubMed ID:8132768 [Hollak1994]
  13. Kzhyshkowska J, Gratchev A, and Goerdt S. (2007). Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. Biomark Insights. 2007;2:128-46. | Google Books | Open Library PubMed ID:19662198 [Kzhyshkowska2007]
  14. Gordon-Thomson C, Kumari A, Tomkins L, Holford P, Djordjevic JT, Wright LC, Sorrell TC, and Moore GP. (2009). Chitotriosidase and gene therapy for fungal infections. Cell Mol Life Sci. 2009;66(6):1116-25. DOI:10.1007/s00018-009-8765-7 | PubMed ID:19169854 [Gordon-Thomson2009]
  15. Joosten MH, Vogelsang R, Cozijnsen TJ, Verberne MC, and De Wit PJ. (1997). The biotrophic fungus Cladosporium fulvum circumvents Cf-4-mediated resistance by producing unstable AVR4 elicitors. Plant Cell. 1997;9(3):367-79. DOI:10.1105/tpc.9.3.367 | PubMed ID:9090881 [Joosten1997]
  16. van den Burg HA, Harrison SJ, Joosten MH, Vervoort J, and de Wit PJ. (2006). Cladosporium fulvum Avr4 protects fungal cell walls against hydrolysis by plant chitinases accumulating during infection. Mol Plant Microbe Interact. 2006;19(12):1420-30. DOI:10.1094/MPMI-19-1420 | PubMed ID:17153926 [Burg2006]

All Medline abstracts: PubMed