7dpx
From Proteopedia
Crystal structure of the SRCR domain of human SCARA1/CD204
Structural highlights
DiseaseMSRE_HUMAN NON RARE IN EUROPE: Barrett esophagus;Familial prostate cancer. The disease may be caused by variants affecting the gene represented in this entry. MSR1 variants may play a role in susceptibility to prostate cancer. MSR1 variants have been found in individuals with prostate cancer and co-segregate with the disease in some families. The disease may be caused by variants affecting the gene represented in this entry. Genetic variants in MSR1 have been found in individuals with Barrett esophagus and are thought to contribute to disease susceptibility. FunctionMSRE_HUMAN Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL) (PubMed:2251254). Isoform III does not internalize acetylated LDL (PubMed:9548586).[1] [2] Publication Abstract from PubMedScavenger receptor class A (SR-A) proteins are type II transmembrane glycoproteins that form homotrimers on the cell surface. This family has five known members (SCARA1 to 5, or SR-A1 to A5) that recognize a variety of ligands and are involved in multiple biological pathways. Previous reports have shown that some SR-A family members can bind modified low-density lipoproteins (LDL); however, the mechanisms of the interactions between the SR-A members and these lipoproteins are not fully understood. Here we systematically characterize the recognition of SR-A receptors with lipoproteins and report that SCARA1 (SR-A1, CD204), MARCO (SCARA2), and SCARA5 recognize acetylated or oxidized LDL and very low-density lipoproteins (VLDL) in a Ca(2+)-dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apoB component of the lipoproteins, suggesting that they might share a similar mechanism for lipoprotein recognition. Meanwhile, SCARA4, a SR-A member with a carbohydrate recognition domain instead of the SRCR domain at the C-terminus, shows low affinity for modified LDL and VLDL, but binds in a Ca(2+)-independent manner. SCARA3, which does not have a globular domain at the C-terminus, was found to have no detectable binding with these lipoproteins. Taken together, these results provide mechanistic insights into the interactions between SR-A family members and lipoproteins that may help us to understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis. Recognition of lipoproteins by scavenger receptor class A members.,Cheng C, Zheng E, Yu B, Zhang Z, Wang Y, Liu Y, He Y J Biol Chem. 2021 Jul 9:100948. doi: 10.1016/j.jbc.2021.100948. PMID:34252459[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
