Structural basis of sequence-specific collagen recognition by SPARC
Structural basis of sequence-specific collagen recognition by SPARC
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DOI：
10.1073/pnas.0808452105
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发表时间：
2008-11-25
影响因子：
11.1
通讯作者：
Baechinger, Hans Peter
中科院分区：
文献类型：
--
作者：
Hohenester, Erhard;Sasaki, Takako;Baechinger, Hans Peter
蛋白质与胶原蛋白三螺旋的相互作用在胶原纤维形成、细胞粘附和信号传导中起着关键作用。然而，对序列特异性胶原蛋白识别的结构洞察仅限于整合素-肽复合物。纤维性胶原中的GVMGFO基序（0表示4-羟脯氨酸）结合3种不相关的蛋白：血管性血液病因子（VWF）、盘状蛋白结构域受体2 （DDR2）和细胞外基质蛋白SPARC/骨连接蛋白/BM-40。我们报道了人类SPARC在3.2埃分辨率下与含有混杂GVMGFO基序的三螺旋33残基肽结合的晶体结构。SPARC识别中间和尾部胶原链的GVMGFO基序，共覆盖720埃(2)的溶剂可溶胶原表面。SPARC结合不会扭曲胶原肽的典型三螺旋结构。相比之下，SPARC中的一个关键环在胶原蛋白结合时基本上被重塑，形成一个深袋，可容纳尾随胶原蛋白链的苯丙氨酸残基（“Phe袋”）。这种高度限制性的特异性口袋与胶原结合整合素i结构域共享，但与血小板受体糖蛋白VI和微生物粘附素的浅胶原结合凹槽明显不同。我们推测GVMGFO基序与VWF和DDR2的结合也会导致结构变化和Phe口袋的形成。
Protein interactions with the collagen triple helix play a critical role in collagen fibril formation, cell adhesion, and signaling. However, structural insight into sequence-specific collagen recognition is limited to an integrin-peptide complex. A GVMGFO motif in fibrillar collagens (0 denotes 4-hydroxyproline) binds 3 unrelated proteins: von Willebrand factor (VWF), discoidin domain receptor 2 (DDR2), and the extracellular matrix protein SPARC/osteonectin/BM-40. We report the crystal structure at 3.2 angstrom resolution of human SPARC bound to a triple-helical 33-residue peptide harboring the promiscuous GVMGFO motif. SPARC recognizes the GVMGFO motifs of the middle and trailing collagen chains, burying a total of 720 angstrom(2) of solvent-accessible collagen surface. SPARC binding does not distort the canonical triple helix of the collagen peptide. In contrast, a critical loop in SPARC is substantially remodelled upon collagen binding, creating a deep pocket that accommodates the phenylalanine residue of the trailing collagen chain ("Phe pocket"). This highly restrictive specificity pocket is shared with the collagen-binding integrin I-domains but differs strikingly from the shallow collagen-binding grooves of the platelet receptor glycoprotein VI and microbial adhesins. We speculate that binding of the GVMGFO motif to VWF and DDR2 also results in structural changes and the formation of a Phe pocket.