Three-dimensional Solution Structure and Conformational Plasticity of the N-terminal Scavenger Receptor Cysteine-rich Domain of Human CD5

Garza-Garcia, Acely; Esposito, Diego; Rieping, Wolfgang; Harris, Richard; Briggs, Cherry; Brown, Marion H.; Driscoll, Paul C.

doi:10.1016/j.jmb.2008.02.006

Cited by 15 publications

(17 citation statements)

References 68 publications

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“…It should be noted that group B SRCR domains of only one protein have been crystallized to date, corresponding to the most membrane-proximal (D3) (Rodamilans et al, 2007) and distal (D1) SRCR domains (Garza-Garcia et al, 2008) of CD5. It is noteworthy that, on the basis of the available data, the basic three-dimensional structure characteristics of group A and B SRCR domains seem to be superimposable and therefore indistinguishable, which makes it questionable to maintain the existence of two different types of SRCR domains from the structural point of view.…”

Section: B Structure Of the Scavenger Receptor Cysteine-rich Domainsmentioning

confidence: 99%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Moestrup²,

et al. 2011

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Section: B Structure Of the Scavenger Receptor Cysteine-rich Domainsmentioning

confidence: 99%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Moestrup²,

et al. 2011

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“…The presence of short Pro, Ser, and Thr (PST)-rich polypeptides interspaced with contiguous SRCR domains is also frequently observed among SRCR-SF members. Available three-dimensional structures obtained from crystallization experiments indicate that group A and B SRCR domains present a highly conserved and compact core folding (a curved six-stranded b sheet cradling an a helix) with variable outer loop regions, likely giving rise to functional diversity (8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Miró-Julià

Roselló

Martínez

et al. 2011

The Journal of Immunology

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The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ∼100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization of mouse S5D-SRCRB, a new group B member of the SRCR-SF. The s5d-srcrb gene maps at mouse chromosome 7 and encompasses 14 exons extending over 15 kb. The longest cDNA sequence found is 4286 bp in length and encodes a mature protein of 1371 aa, with a predicted Mr of 144.6 kDa. Using an episomal mammalian-expression system, a glycosylated soluble recombinant form >200 kDa was obtained and used as immunogen for the generation of specific rat mAbs. Subsequent immunohistochemical and real-time PCR analysis showed significant S5D-SRCRB expression in murine genitourinary and digestive tracts. S5D-SRCRB was shown to bind endogenous extracellular matrix proteins (laminin and galectin-1), as well as PAMPs present on Gram-positive and Gram-negative bacteria and fungi. PAMP binding by S5D-SRCRB induced microbial aggregation and subsequent inhibition of PAMP-induced cytokine release. These abilities suggest that S5D-SRCRB might play a role in the innate defense and homeostasis of certain specialized epithelial surfaces.

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“…Ab9, Ab15 and Ab18 all target non‐overlapping epitopes on domain 1. The majority of the murine mAbs known to induce CD5 internalizing have been mapped to CD5 domain 1 (Martin et al , ; McAlister et al , ; Calvo et al , ; Garza‐Garcia et al , ). Although none of the individual chimeric mAbs in these studies induced significant CD5 internalization, all the combinations of mAbs that induced high levels of CD5 internalization, bind epitopes on domain 1.…”

Section: Discussionmentioning

confidence: 99%

Combination of two anti‐CD5 monoclonal antibodies synergistically induces complement‐dependent cytotoxicity of chronic lymphocytic leukaemia cells

et al. 2013

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SummaryThe treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two mAbs significantly increased the level of CDC compared to the single mAbs, while no enhancement of ADCC was seen with anti-CD5 mAb combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. These results suggest that an anti-CD5 mAb combination inducing CDC and ADCC may be effective alone, in combination with mAbs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies.

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Three-dimensional Solution Structure and Conformational Plasticity of the N-terminal Scavenger Receptor Cysteine-rich Domain of Human CD5

Cited by 15 publications

References 68 publications

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Combination of two anti‐CD5 monoclonal antibodies synergistically induces complement‐dependent cytotoxicity of chronic lymphocytic leukaemia cells

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