Molecular modelling of the immunoglobulin‐like domains of the neural cell adhesion molecule (NCAM): Implications for the positioning of functionally important sugar side chains

Molecular modelling of the immunoglobulin‐like domains of the neural cell adhesion molecule (NCAM): Implications for the positioning of functionally important sugar side chains
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神经细胞粘附分子 (NCAM) 的免疫球蛋白样结构域的分子建模:对功能上重要的糖侧链定位的影响

DOI:
10.1002/jnr.490200304
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发表时间:
1988
影响因子:
4.2
通讯作者:
J. Fontecilla
J. Fontecilla
中科院分区:
医学3区
文献类型:
--
作者:
M. Santoni;C. Goridis;J. Fontecilla

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神经细胞粘附分子(NCAM)被认为通过涉及位于蛋白质N末端区域的结合位点的嗜同性机制介导细胞间粘附。分子的该区域由五个结构域组成,它们彼此同源并且与免疫球蛋白结构域共享保守残基。我们在这里报告了五个NCAM结构域的二级结构预测和其中两个的三维模型。结果与NCAM结构域的免疫球蛋白样折叠成形成两个B折叠的七条链完全一致。因此,NCAM-NCAM结合可能类似于免疫球蛋白恒定结构域的成对缔合,其参与二聚体形成。插入和缺失主要位于B转角区域。在第三和第四结构域中的两个α螺旋区域被预测具有高概率。NCAM具有两种功能上重要的糖侧链,第五结构域中的唾液酸聚合物,其调节NCAM结合,以及L2部分,其参与细胞粘附并且可以被分配到第三结构域。相应结构域的三维建模表明,第五个结构域中的三个N-连接糖基化位点中的两个和第三个结构域中的单个位点位于结构域的表面上,其在免疫球蛋白恒定区中参与分子间相互作用。
The neural cell adhesion molecule (NCAM) is thought to mediate cell–cell adhesion by a homophilic mechanism involving binding sites located in the N‐terminal region of the protein. This region of the molecule consists of five domains that are homologous to each other and share conserved residues with immunoglobulin domains. We report here secondary structure predictions for the five NCAM domains and three‐dimensional models for two of them. The results are entirely consistent with an immunoglobulin‐like folding of the NCAM domains into seven strands forming two b̃‐sheets. NCAM–NCAM binding may thus be analogous to the pairwise associations of immunoglobulin constant domains, which are involved in dimer formation. Insertions and deletions are located mostly in b̃‐turn regions. Two α‐helical regions in the third and fourth domain are predicted with high probability. NCAM bears two kinds of functionally important sugar side chains, sialic acid polymers in the fifth domain, which modulate NCAM binding, and the L2 moiety, which is involved in cell adhesion and can be assigned to the third domain. Three‐dimensional modelling of the corresponding domains indicates that two of the three sites for N‐linked glycosylation in the fifth and the single site in the third domain are located on he face of the domain, which in immunoglobulin contant regions engages in intermolecular interactions.
DOI: 10.1126/science.3576199
发表时间: 1987-05-15
期刊: SCIENCE
影响因子: 56.9
作者:
CUNNINGHAM, BA;HEMPERLY, JJ;EDELMAN, GM
通讯作者: EDELMAN, GM
DOI: 10.1016/0041-0101(82)90137-4
发表时间: 1982
期刊: Toxicon : official journal of the International Society on Toxinology
影响因子: --
作者:
Fontecilla-Camps,JC;Almassy,RJ;Suddath,FL;Bugg,CE
通讯作者: Bugg,CE
DOI: 10.1073/pnas.80.10.3116
发表时间: 1983-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
CUNNINGHAM, BA;HOFFMAN, S;EDELMAN, GM
通讯作者: EDELMAN, GM