Molecular analysis and solution structure from small-angle X-ray scattering of the human natural killer inhibitory receptor IRp60 (CD300a)

The CD300 family of molecules are evolutionarily significant regulators of leukocyte functions

“…The IgV domain structures of CD300a and CD300f have been confirmed by crystallization [11][12][13]. The transmembrane domains of CD300b, CD300c, CD300d, and CD300e contain a charged amino acid residue, which enables association with other transmembrane molecules, for example, adaptor molecules such as DAP12, whereas the cytoplasmic domains of CD300a and CD300f contain tyrosine-based signalling motifs, for example, the immunoreceptor tyrosine-based inhibitory motif (ITIM).…”

“…MDIR are members of a multigene family of stimulatory and inhibitory Ig super family receptors [19]. Of note, the CD300 Ig-like fold has conserved an amino acid motif, YWCR, and two (instead of one) disulfide bonds, indicating strong evolutionary pressure to maintain CD300-like domains from ancient vertebrates onwards [11,13]. The CD300 molecules are also distant relatives of the Fc receptor for polymeric IgA and IgM [3], the TREM molecules and CD336 (NKp46) [20], which also contain two disulfide bonds within their IgV domains, defining a novel group of Ig superfamily molecules with common ancestry.…”

The CD300 molecules: an emerging family of regulators of the immune system

“…85 To identify the residues that are involved in human CD300a binding to PS and PE, a molecular model was generated based on the crystal structure of TIM-4 complexed with PS. 76,86 The crystal structure of human CD300a is known, 14 and the metal ion and a molecule of PS or PE were placed in positions corresponding to the PS bound to TIM-4 structure. The model showed that PE and PS interact with CD300a residues that form a cavity where the hydrophilic heads of the lipids can penetrate.…”

“…9,14,15 Only CD300a and CD300f have long cytoplasmic tails with ITIMs, whereas the other members have a short cytoplasmic tail and a charged transmembrane residue and associate with adaptor proteins such as DNAX associated protein (DAP)12, DAP10, and the Fc receptor (FcR)g chain (FceRIg) 9 ( Figure 2). One exception is CD300g, which is encoded by a gene mapped at some distance from the complex, lacks structural motifs suggestive of stimulatory or inhibitory potential, and in addition to the IgV-like domain, has a mucin-like domain.…”

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

“…To identify the residues that are involved in human CD300a binding to PS and PE, a molecular model was generated based on the crystal structure of T cell/ transmembrane, Ig, and mucin (TIM)-4 complexed with PS (38,46). The metal ion and a molecule of PS or PE were placed in positions corresponding to the PS bound to the TIM-4 structure in the crystal structure of CD300a (38,47). The model showed that PE and PS interact with CD300a residues that form a cavity into which the hydrophilic heads of the lipids can penetrate (38).…”