Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors.
Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors.
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DOI：
10.7554/elife.38362
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发表时间：
2018-10-15
期刊：
影响因子：
7.7
通讯作者：
Steiner RA
中科院分区：
文献类型：
--
作者：
Pernigo S;Chegkazi MS;Yip YY;Treacy C;Glorani G;Hansen K;Politis A;Bui S;Dodding MP;Steiner RA
异源四聚体微管运动驱动蛋白-1的轻链（KLC）与货物衔接蛋白结合并调节其活性，具有通过其三肽重复结构域（KLCTPR）识别短肽的能力。在这里，使用X-射线晶体学，我们展示了驱动蛋白-1如何识别一类新的衔接基序，我们称之为“Y-酸性”（酪氨酸侧翼的酸性残基），在一个KLC亚型的具体方式。Y-酸性基序（存在于JIP 1和TorsinA中）与KLC 1 TPR的结合特异性不同于用于识别KLC-亚型非选择性衔接子中发现的W-酸性基序的特异性。然而，在它们的受体结合位点上的部分重叠意味着依赖于Y-酸性基序和W-酸性基序的衔接子必须独立地起作用。我们提出了一个模型来解释为什么这两类图案结合到凹面KLCTPR具有类似的低微摩尔亲和力可以表现出不同的能力，以促进驱动蛋白-1的活性。
The light chains (KLCs) of the heterotetrameric microtubule motor kinesin-1, that bind to cargo adaptor proteins and regulate its activity, have a capacity to recognize short peptides via their tetratricopeptide repeat domains (KLCTPR). Here, using X-ray crystallography, we show how kinesin-1 recognizes a novel class of adaptor motifs that we call ‘Y-acidic’ (tyrosine flanked by acidic residues), in a KLC-isoform specific manner. Binding specificities of Y-acidic motifs (present in JIP1 and in TorsinA) to KLC1TPR are distinct from those utilized for the recognition of W-acidic motifs found in adaptors that are KLC- isoform non-selective. However, a partial overlap on their receptor binding sites implies that adaptors relying on Y-acidic and W-acidic motifs must act independently. We propose a model to explain why these two classes of motifs that bind to the concave surface of KLCTPR with similar low micromolar affinity can exhibit different capacities to promote kinesin-1 activity.