8HLO

Crystal structure of ASAP1-SH3 and MICAL1-PRM complex

Summary for 8HLO

• Entry DOI: 10.2210/pdb8hlo/pdb
• Descriptor: Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1, Proline rich motif from MICAL1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: sh3, proline-rich motif, high-affinity, protein binding
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 9041.90

Authors

Niu, F.,Wei, Z.,Yu, C. (deposition date: 2022-11-30, release date: 2023-02-22, Last modification date: 2024-05-29)

Primary citation

Jia, X.,Lin, L.,Xu, S.,Li, L.,Wei, Z.,Yu, C.,Niu, F.
Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: SH3 domains are common protein binding modules. The target sequence of SH3 domains is usually a proline-rich motif (PRM) containing a minimal "PxxP" sequence. The mechanism of how different SH3 domains specifically choose their targets from vast PxxP-containing sequences is still not very clear, as many reported SH3/PRM interactions are weak and promiscuous. Here, we identified the binding of the SH3 domain of ASAP1 to the PRM of MICAL1 with a sub-μM binding affinity, and determined the crystal structure of ASAP1-SH3 and MICAL1-PRM complex. Our structural and biochemical analyses revealed that the target-binding pocket of ASAP1-SH3 contains two negatively charged patches to recognize the "xPx + Px+" sequence in MICAL1-PRM and consequently strengthen the interaction, differing from the typical SH3/PRM interaction. This unique PRM-binding pocket is also found in the SH3 domains of GTPase Regulator associated with focal adhesion kinase (GRAF) and Src kinase associated phosphoprotein 1 (SKAP1), which we named SH3. In addition, we searched the Swiss-Prot database and found ~130 proteins with the SH3-binding PRM in silico. Finally, gene ontology analysis suggests that the strong interaction between the SH3-containing proteins and their targets may play roles in actin cytoskeleton regulation and vesicle trafficking.

PubMed: 36674928
DOI: 10.3390/ijms24021414

Experimental method

X-RAY DIFFRACTION (1.168 Å)