{"doi":"10.1101/2024.02.01.578455","title":"<i>α</i> <sub>M</sub> I-domain of Integrin Mac-1 Binds the Cytokine Pleiotrophin Using Multiple Mechanisms","abstract":"SUMMARY The integrin Mac-1 (α M β 2 , CD11b/CD18, CR3) is an important adhesion receptor expressed on macrophages and neutrophils. Mac-1 is also the most promiscuous member of the integrin family that binds a diverse set of ligands through its α M I-domain. However, the binding mechanism of most ligands is not clear. We have determined the interaction of α M I-domain with the cytokine pleiotrophin (PTN), a cationic protein known to bind α M I-domain and induce Mac-1-mediated cell adhesion and migration. Our data show that PTN’s N-terminal domain binds a unique site near the N- and C-termini of the α M I-domain using a metal-independent mechanism. However, stronger interaction is achieved when an acidic amino acid in a zwitterionic motif in PTN’s C-terminal domain chelates the divalent cation in the metal ion-dependent adhesion site of the active α M I-domain. These results indicate that α M I-domain can bind ligands using multiple mechanisms, and suggest that active α M I-domain prefers acidic amino acids in zwitterionic motifs. HIGHLIGHTS α M I-domain’s interaction with the cytokine pleiotrophin (PTN) was investigated with solution NMR. α M I-domain binds PTN using multiple mechanisms. PTN’s N-terminal domain binds both active and inactive α M I-domains using a unique site near α M I-domain’s termini. PTN’s C-terminal domain binds only active α M I-domain through a metal-dependent interaction.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":494391,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425153,"name":"Nataly P. Podolnikova","orcid":null,"position":1,"is_corresponding":false},{"id":423798,"name":"Tatiana P. Ugarova","orcid":"0000-0003-4449-5140","position":2,"is_corresponding":false},{"id":337596,"name":"Xu Wang","orcid":"0000-0001-8428-9339","position":3,"is_corresponding":false},{"id":795386,"name":"Hoa Phuoc Trung Nguyen","orcid":"0000-0001-6908-807X","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:09:11.736910Z","pmid":"38352421","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}