7DPX

Crystal structure of the SRCR domain of human SCARA1/CD204

Summary for 7DPX

• Entry DOI: 10.2210/pdb7dpx/pdb
• Descriptor: Macrophage scavenger receptor types I and II, CALCIUM ION (3 entities in total)
• Functional Keywords: scavenger receptor class a, modified lipoprotein (s), apob, srcr domain, ldl, vldl, scara1, endocytosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12478.04

Authors

Cheng, C.,He, Y. (deposition date: 2020-12-21, release date: 2021-07-28, Last modification date: 2024-10-23)

Primary citation

Cheng, C.,Zheng, E.,Yu, B.,Zhang, Z.,Wang, Y.,Liu, Y.,He, Y.
Recognition of lipoproteins by scavenger receptor class A members.
J.Biol.Chem., 297:100948-100948, 2021

PubMed Abstract: Scavenger 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 (LDLs); 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 lipoprotein in a Ca-dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apolipoprotein B 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 very-low-density lipoprotein but binds in a Ca-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 understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis.

PubMed: 34252459
DOI: 10.1016/j.jbc.2021.100948

Experimental method

X-RAY DIFFRACTION (2.002 Å)