Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

Holmskov, Uffe; Mollenhauer, Jan; Madsen, Jens; Vitved, Lars; Grønlund, Jørn; Tornøe, Ida; Kliem, Anette; Poustka, Annemarie; Skjødt, Karsten

doi:10.1073/pnas.96.19.10794

Cited by 190 publications

(264 citation statements)

References 30 publications

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“…Due to the highly repetitive nature of A [1][2][3] , it is plausible that adherence-inhibiting antibodies recognize a repeated epitope and disrupt the binding via steric hindrance. SAG's gp340 also contains multiple tandem repeats of scavenger receptor cysteine-rich (SRCR) domains (38). Although a structure of tandem repeats of these SRCR domains has not been determined, gp340 may be reminiscent of fibronectin, whose repeated domains display an elongated structure (39).…”

Section: Discussionmentioning

confidence: 99%

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of α- and PPII-helices

Larson

Rajashankar

Patel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

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Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein adhesin that interacts with salivary components within the salivary pellicle. AgI/II contributes to virulence and has been studied as an immunological and structural target, but a fundamental understanding of its underlying architecture has been lacking. Here we report a high-resolution (1.8 Å) crystal structure of the A 3 VP 1 fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 Å) through the interaction of two noncontiguous regions in the primary sequence. The A 3 repeat of the alanine-rich domain adopts an extended α-helix that intertwines with the P 1 repeat polyproline type II (PPII) helix to form a highly extended stalk-like structure heretofore unseen in prokaryotic or eukaryotic protein structures. Velocity sedimentation studies indicate that fulllength AgI/II that contains three A/P repeats extends over 50 nanometers in length. Isothermal titration calorimetry revealed that the high-affinity association between the A 3 and P 1 helices is enthalpically driven. Two distinct binding sites on AgI/II to the host receptor salivary agglutinin (SAG) were identified by surface plasmon resonance (SPR). The current crystal structure reveals that AgI/II family proteins are extended fibrillar structures with the number of alanine-and proline-rich repeats determining their length.bacterial adhesion | dental caries | Streptococcus | x-ray crystallography | fibrous proteins S treptococcus mutans is the causative agent of human dental caries (1) and its protein adhesin antigen I/II (AgI/II) is a known target of protective immunity (2). AgI/II family molecules are expressed by numerous oral streptococci (3) and homologs have also been identified in the invasive pathogens Streptococcus pyogenes and Streptococcus agalactiae (4) (Fig. S1). In addition to mediating adhesion to the tooth surface (5), AgI/II influences biofilm formation (6), promotes collagen-dependent bacterial invasion of dentin (7), and mediates adherence to human epithelial cells (8). Elimination of AgI/II results in decreased virulence (9), but despite three decades of study, a mechanistic understanding of the functional properties of the molecule has been stymied by a lack of understanding of its structure.Originally identified as AgI/II (10) (also called P1, PAc, or SpaP), members of this protein family contain between 1310 and 1653 amino acids (aa) beginning with an amino-terminal signal motif that directs secretion, followed by the A, V, and P regions (Fig. 1A). The A region typically consists of 3-4 alanine-rich repeats (82 residues each) with 23-30% alanine content. The P region has 3-4 proline-rich repeats (39 residues each) with ∼35% proline content. Nested between the A and P repeats is a segment commonly referred to as the V or variable region, which contains within it a stretch of ∼100 amino acids where most of the sequence variation among S. mutans AgI/II molecules is clustered (11). The crystal structure of the V region adopts a globular β-s...

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Section: Discussionmentioning

confidence: 99%

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of α- and PPII-helices

Larson

Rajashankar

Patel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

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“…In mice, Muclin is most strongly expressed in the gastrointestinal system, including pancreas [weaker in human pancreas (21)], gallbladder, salivary glands, crypts throughout the small and large intestines (12), and nasal/olfactory/vomeronasal epithelium (29,33). It has also been detected weakly in the kidney and liver (53).…”

mentioning

confidence: 99%

“…DMBT1 gene expression in humans is strong in lung [weaker in mouse (12)]; at weak levels in brain (21,37); at strong levels in salivary glands (16,29,42); and at weak levels in mammary gland, uterus, testis, and prostate (21). In addition to these tissues, the protein has been detected in human tear fluid (48), sweat glands, hair follicles and epidermis (35), liver (47), alveolar macrophages (21), pancreatic juice (18), bile (28), and airway submucosal gland secretions (49). In general, the gene is expressed most strongly in epithelia and is usually observed on the apical cell surface or in luminal exocrine secretions.…”

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confidence: 99%

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

Lisle

Xu²,

Roe³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…SRCR proteins, e.g. the macrophage scavenger receptor, Mac-2-binding protein, CD5, CD6, WC1, Ebnerin, CRP (cyclic AMP receptor protein)-ductin, and lung gp-340, are associated with host defense systems (7,8,(11)(12)(13)(14)(15)(16)(17). Until now, studies dealing with agglutinin-bacteria interactions have been focused mainly on the characterization of bacterial receptors (18,19) and identification of their cognate carbohydrate ligands on agglutinin (1, 20 -22).…”

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confidence: 99%

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

Bikker¹,

Ligtenberg²,

Nazmi³

et al. 2002

Journal of Biological Chemistry

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145

183

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Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/ DMBT1 is known for its Streptococcus mutans agglutinating properties. This 300 -400 kDa glycoprotein is composed of conserved peptide motifs: 14 SRCR domains that are separated by SRCR-interspersed domains (SIDs), 2 CUB (C1r/C1s Uegf Bmp1) domains, and a zona pellucida domain. We have searched for the peptide domains of agglutinin/DMBT1 responsible for bacteria binding. Digestion with endoproteinase Lys-C resulted in a protein fragment containing exclusively SRCR and SID domains that binds to S. mutans. To define more closely the S. mutans-binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S. mutans. Strikingly, this peptide was also able to induce agglutination of S. mutans and a number of other bacteria. The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character. Moreover, our studies demonstrate for the first time that the polymorphic SRCR domains of salivary agglutinin/DMBT1 mediate ligand interactions.

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Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

Abstract: Surfactant protein D (SP-D) is an oligomeric

Cited by 190 publications

References 30 publications

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of α- and PPII-helices

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of α- and PPII-helices

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

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