Linked Life Data

14693915

Source:http://linkedlifedata.com/resource/pubmed/id/14693915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-4-8
pubmed:databankReference
pubmed:abstractText
Most mammalian cell surfaces display two major sialic acids (Sias), N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Humans lack Neu5Gc due to a mutation in CMP-Neu5Ac hydroxylase, which occurred after evolutionary divergence from great apes. We describe an apparent consequence of human Neu5Gc loss: domain-specific functional adaptation of Siglec-9, a member of the family of sialic acid-binding receptors of innate immune cells designated the CD33-related Siglecs (CD33rSiglecs). Binding studies on recombinant human Siglec-9 show recognition of both Neu5Ac and Neu5Gc. In striking contrast, chimpanzee and gorilla Siglec-9 strongly prefer binding Neu5Gc. Simultaneous probing of multiple endogenous CD33rSiglecs on circulating blood cells of human, chimp, or gorilla suggests that the binding differences observed for Siglec-9 are representative of multiple CD33rSiglecs. We conclude that Neu5Ac-binding ability of at least some human CD33rSiglecs is a derived state selected for following loss of Neu5Gc in the hominid lineage. These data also indicate that endogenous Sias (rather than surface Sias of bacterial pathogens) are the functional ligands of CD33rSiglecs and suggest that the endogenous Sia landscape is the major factor directing evolution of CD33rSiglec binding specificity. Exon-1-encoded Sia-recognizing domains of human and ape Siglec-9 share only approximately 93-95% amino acid identity. In contrast, the immediately adjacent intron and exon 2 have the approximately 98-100% identity typically observed among these species. Together, our findings suggest ongoing adaptive evolution specific to the Sia-binding domain, possibly of an episodic nature. Such domain-specific divergences should also be considered in upcoming comparisons of human and chimpanzee genomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0959-6658
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
339-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14693915-Amino Acid Sequence, pubmed-meshheading:14693915-Animals, pubmed-meshheading:14693915-Antigens, CD, pubmed-meshheading:14693915-Evolution, Molecular, pubmed-meshheading:14693915-Hominidae, pubmed-meshheading:14693915-Humans, pubmed-meshheading:14693915-Lectins, pubmed-meshheading:14693915-Ligands, pubmed-meshheading:14693915-Molecular Sequence Data, pubmed-meshheading:14693915-N-Acetylneuraminic Acid, pubmed-meshheading:14693915-Phylogeny, pubmed-meshheading:14693915-Protein Structure, Tertiary, pubmed-meshheading:14693915-Receptors, Cell Surface, pubmed-meshheading:14693915-Selection, Genetic, pubmed-meshheading:14693915-Sequence Homology, Amino Acid, pubmed-meshheading:14693915-Species Specificity, pubmed-meshheading:14693915-Structure-Activity Relationship, pubmed-meshheading:14693915-Substrate Specificity
pubmed:year
2004
pubmed:articleTitle
A uniquely human consequence of domain-specific functional adaptation in a sialic acid-binding receptor.
pubmed:affiliation
Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0687, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't