Structure and Function of Choline-Binding Proteins

Galán-Bartual, Sergio; Pérez‐Dorado, Inmaculada; García, Pedro; Hermoso, J.A.

doi:10.1016/b978-0-12-410530-0.00011-9

Cited by 24 publications

(36 citation statements)

References 106 publications

(120 reference statements)

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“…Structural and sequence analyses revealed that among the nine choline-binding repeats (R1-R9), none of them follows the consensus sequence GWXK-X 4–5 -WYY-φ-X 3–5 GXMX 2–3 , where X is any residue and φ is hydrophobic, as observed for other CBPs1617. Instead, the repeats can be grouped in two main classes: the long repeats (21 to 23 residues-long; R1, R3, R5, R7 and R9) and the short repeats (17 residues-long; R2, R4, R6, R8) (Fig.…”

Section: Resultsmentioning

confidence: 84%

“…3A). CbpL CBM is folded in a left-handed superhelical arrangement of the choline-binding repeats, each of them comprising a β-hairpin followed by a loop and a coiled region that is linked to the next repeat, as previously reported in other CBPs15161726. The β-hairpin units stack along the structure (from N to C-terminal end) following a 120° counterclockwise rotation in such a way that choline-binding sites are formed at the interface of two consecutive β-hairpins.…”

Section: Resultsmentioning

confidence: 88%

“…CbpL is the only one having the CBM sandwiched between two functional modules located at both extremes. In CBPs the CBM is composed of three to eighteen repeated sequences of approximately 20 amino acids forming the different choline-binding sites17. These sites are integrated by specific configurations of aromatic residues that stabilize the choline molecules from WTA and LTA through cation- π interactions18.…”

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confidence: 99%

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Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

Gutiérrez-Fernández

Saleh

Alcorlo

et al. 2016

Sci Rep

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The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca2+-binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp_Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 88%

mentioning

confidence: 99%

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Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

Gutiérrez-Fernández

Saleh

Alcorlo

et al. 2016

Sci Rep

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“…In this respect, it is also worth mentioning that the majority of the CBRs found in the CBPs of Gemella spp. does not follow the consensus sequence of most pneumococcal CBPs: GWxK-X 4−5 -WYY-ϕ-x 3−5 GxMx 2−3 , where x is any residue and ϕ is hydrophobic (Galán-Bartual et al, 2015). Instead, the CBRs of Gemellae consist of a series of long and short repeats that are strikingly similar to those reported only in CbpL, a CBP with relevance in pneumococcal pathogenesis (Gutiérrez-Fernández et al, 2016) (Supplementary Figure S2).…”

Section: Phosphorylcholine and Choline-binding Proteins In The Cell Wmentioning

confidence: 73%

The Versatility of Opportunistic Infections Caused by Gemella Isolates Is Supported by the Carriage of Virulence Factors From Multiple Origins

López

Martín-Galiano

2020

Front. Microbiol.

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The molecular basis of the pathogenesis of the opportunistic invasive infections caused by isolates of the Gemella genus remains largely unknown. Moreover, inconsistencies in the current species assignation were detected after genome-level comparison of 16 public Gemella isolates. A literature search detected that, between the two most pathogenic species, Gemella morbillorum causes about twice the number of cases compared to Gemella haemolysans. These two species shared their mean diseasessepsis and endocarditis-but differed in causing other syndromes. A number of well-known virulence factors were harbored by all species, such as a manganese transport/adhesin sharing 83% identity from oral endocarditis-causing streptococci. Likewise, all Gemellae carried the genes required for incorporating phosphorylcholine into their cell walls and encoded some choline-binding proteins. In contrast, other proteins were species-specific, which may justify the known epidemiological differences. G. haemolysans, but not G. morbillorum, harbor a gene cluster potentially encoding a polysaccharidic capsule. Species-specific surface determinants also included Rib and MucBP repeats, hemoglobin-binding NEAT domains, peptidases of C5a complement factor and domains that recognize extracellular matrix molecules exposed in damaged heart valves, such as collagen and fibronectin. Surface virulence determinants were associated with several taxonomically dispersed opportunistic genera of the oral microbiota, such as Granulicatella, Parvimonas, and Streptococcus, suggesting the existence of a horizontally transferrable gene reservoir in the oral environment, likely facilitated by close proximity in biofilms and ultimately linked to endocarditis. The identification of the Gemella virulence pool should be implemented in whole genomebased protocols to rationally predict the pathogenic potential in ongoing clinical infections caused by these poorly known bacterial pathogens.

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“…On the other hand, the basic repeating unit for TA is comprised of 2-acetamido-4-amino-2,4,6-trideoxy- d -galactose, d -glucose, ribitol-phosphate and two residues of N -acetylgalactosamine (GalNAc) [ 26 , 31 , 32 , 33 ] ( Figure 1 ), whereas glucose is replaced by galactose in the TA of a serotype 5 strain [ 34 ]. Either one or both of the GalNAc residues (depending on the strain) are modified with phosphorylcholine (P-Cho) [ 31 , 35 , 36 ], an amino alcohol that can also be found in the surface of several other microorganisms [ 37 , 38 , 39 , 40 ], including pathogens that reside primarily in the mammalian airway [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Choline Binding Proteins from Streptococcus pneumoniae: A Dual Role as Enzybiotics and Targets for the Design of New Antimicrobials

2016

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Streptococcus pneumoniae (pneumococcus) is an important pathogen responsible for acute invasive and non-invasive infections such as meningitis, sepsis and otitis media, being the major cause of community-acquired pneumonia. The fight against pneumococcus is currently hampered both by insufficient vaccine coverage and by rising antimicrobial resistances to traditional antibiotics, making necessary the research on novel targets. Choline binding proteins (CBPs) are a family of polypeptides found in pneumococcus and related species, as well as in some of their associated bacteriophages. They are characterized by a structural organization in two modules: a functional module (FM), and a choline-binding module (CBM) that anchors the protein to the choline residues present in the cell wall through non-covalent interactions. Pneumococcal CBPs include cell wall hydrolases, adhesins and other virulence factors, all playing relevant physiological roles for bacterial viability and virulence. Moreover, many pneumococcal phages also make use of hydrolytic CBPs to fulfill their infectivity cycle. Consequently, CBPs may play a dual role for the development of novel antipneumococcal drugs, both as targets for inhibitors of their binding to the cell wall and as active cell lytic agents (enzybiotics). In this article, we review the current state of knowledge about host- and phage-encoded pneumococcal CBPs, with a special focus on structural issues, together with their perspectives for effective anti-infectious treatments.

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Structure and Function of Choline-Binding Proteins

Cited by 24 publications

References 106 publications

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

The Versatility of Opportunistic Infections Caused by Gemella Isolates Is Supported by the Carriage of Virulence Factors From Multiple Origins

Choline Binding Proteins from Streptococcus pneumoniae: A Dual Role as Enzybiotics and Targets for the Design of New Antimicrobials

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