Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains

Graves, Bradford; Crowther, R.; Chandran, Chitra; Rumberger, John M.; Li, Shirley Xin; Huang, Kuo‐Sen; Presky, David H.; Familletti, Philip C.; Wolitzky, Barry A.; Burns, Daniel K.

doi:10.1038/367532a0

Cited by 409 publications

(362 citation statements)

References 48 publications

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“…This was long enough to allow the connection to be made, even though the rotation about this link would be arbitrary. A similar link joined the CRD and EGF domains in the crystal structure of E-selectin [17]. The dimensions of the G3 model were 7.0 nmi5.7 nmi3.9 nm.…”

Section: Figure 6 Molecular Model Of the Crd And Scr Domains In G3 Ofmentioning

confidence: 74%

“…In contrast, a survey of known lectincarbohydrate interactions shows that acidic and amide groups commonly form the basis of hydrogen bond formation between protein and carbohydrate hydroxy groups in complex-type and high-mannose-type oligosaccharides [49]. Although Arg-97 and Lys-113 have been implicated in E-selectin adhesion to neutrophils [17], Arg-97 in that study corresponds to the loop between residues 115 and 116 in Figure 2 and is not conserved in Pselectin, whereas Lys-113 corresponds to residue 128 in Figure 2 and is conserved in the selectins and some of the group III CRDs. Neither Arg-97 or Lys-113 corresponds in position to the five conserved basic residues observed in the G3 CRDs (Figure 3).…”

Section: Structure Function and Evolution Of G3 In Proteoglycansmentioning

confidence: 99%

“…Crystal structures are known for mannose-binding protein, Eselectin and lithostathine in the CRD superfamily [15][16][17][18][19][20][21]. To correlate these with the G3 CRD structure, an alignment of 131 CRD sequences is reported in both Figures 2 and 3.…”

Section: Sequence Alignment and Residue Conservation In The Crd Supermentioning

confidence: 99%

“…Crystal structures are known for mannose-binding protein A and C, E-selectin, lithostathine and tetranectin in groups III, IV and VII [15][16][17][18][19][20][21]. The CRD contains a characteristic motif of two α-helices between which are three antiparallel β-strands (β), this motif being attached to three further β-strands in an upper region with two Ca# + -binding sites [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Brissett

Perkins

1998

Biochemical Journal

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Aggrecan is the major proteoglycan of the extracellular matrix in cartilage. It contains two N-terminal globular regions, G1 and G2, and one C-terminal globular region, G3. G3 is implicated in the intracellular processing of aggrecan and contains a C-type lectin carbohydrate recognition domain (CRD), frequent occurrences of a C-terminal short complement repeat (SCR) domain, and occasionally an N-terminal epidermal growth factor domain. The CRD and SCR domains in 13 G3 sequences were each subjected to structural analysis. Alignment of 131 sequences from all seven groups in the CRD superfamily defined a consensus length of 136 residues, in which 32% of residues were conserved. Although the G3 CRD sequences agreed with this consensus, they also contained five fully conserved basic residues that are atypical of the CRD superfamily. Homology modelling showed that four of these residues are located on a surface region on the CRD that is separate from the Ca2+-binding residues involved in carbohydrate interactions. One conserved basic residue is identical in position with that of a conserved basic residue that mediates hyaluronate binding in the structurally related proteoglycan tandem repeat (PTR) domain in G1 and in link protein. The alignment of 13 G3 SCR sequences with 101 sequences in the SCR superfamily showed good agreement with conserved residues in the SCR superfamily. There are also five conserved basic residues in the G3 SCR that are atypical of the SCR superfamily, and homology modelling showed that all five were located on one surface of the SCR. It is concluded that both the CRD and SCR domains in G3 possess basic residues that are atypical of their superfamilies and might be related to function, and that the G3 CRD domain shows an evolutionary relationship to the PTR domain in G1.

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Section: Figure 6 Molecular Model Of the Crd And Scr Domains In G3 Ofmentioning

confidence: 74%

Section: Structure Function and Evolution Of G3 In Proteoglycansmentioning

confidence: 99%

Section: Sequence Alignment and Residue Conservation In The Crd Supermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Brissett

Perkins

1998

Biochemical Journal

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“…The structures of a number of EGF-like domains have been determined, and most of them are consistent with an EGFlike disulfide bonding pattern. [10][11][12][13][14][15][16] On screening 50 CADASIL families for mutations along the entire coding sequence of the Notch3 gene, Joutel et al found mutations in 90% of the families. 17 All mutations were located in one of the 34 EGF-like repeat domains with a strong cluster in two exons coding for the first five repeats.…”

Section: Introductionmentioning

confidence: 99%

Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3v EGF-like repeat domains

Dichgans¹,

Ludwig²,

Müller‐Höcker

et al. 2000

Eur J Hum Genet

113

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CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary microangiopathic condition causing stroke in young adults. The responsible gene has recently been identified as the Notch3 gene. Notch3 encodes a large transmembrane receptor with 34 extracellularly localised epidermal growth factor-like (EGF) repeat domains. We screened 71 unrelated CADASIL families for mutations in two exons coding for the first five EGF-like repeats and found mutations in 70% of the families (n = 50). Two types of mutations were identified: 48 families (96%) had missense mutations and two families (4%) had small in-frame deletions. Seven mutations occurred multiple times. All of them are C to T transitions that affect CpG dinucleotides, suggesting that their multiple occurrence is due to the hypermutability of this sequence. All mutations, including the two deletions, result in the gain or loss of a cysteine residue, thus substantiating the pivotal role of an uneven number of cysteine residues within EGF-like repeat domains of Notch3 in the pathogenesis of CADASIL. To study the potential effects of these mutations 3D homology models of the first six EGF domains were generated on the basis of NMR data from human fibrillin-1. These models predict domain misfolding for a subset of mutations.

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Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions

Bajorath

2000

Proteins

139

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CD44 is a type I transmembrane protein and member of the cartilage link protein family. It is involved in cell-cell and cell-matrix interactions and signal transduction. Several CD44 ligands have been identified. CD44 is a major cell surface receptor for hyaluronan, a component of the extracellular matrix. It is implicated in diseases such as cancer and inflammation and therefore intensely studied. A characteristic feature of CD44 is the occurrence of many isoforms that are expressed in a cell-specific manner and differentially glycosylated. Although a number of CD44 isoforms have been characterized, the structural diversity of CD44 makes it often challenging to study (isoform-specific) CD44-ligand interactions at the molecular level of detail. The structural organization and ligand binding characteristics of CD44 are focal points of this review. On the basis of recent structural and mutagenesis studies, details of the CD44-hyaluronan interaction are beginning to be understood. Proteins 2000;39:103-111.

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Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains

Cited by 409 publications

References 48 publications

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3v EGF-like repeat domains

Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions

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